The DOI matches its Crossref record; 301 of the 302 references it cites were found in a registry or an index; none of the 314 sources its claims cite is checked for support yet.
Pancreatic cancer: Advances and challenges
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Significant efforts have largely defined major genetic factors driving PDAC pathogenesis and progression. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this review, we highlight the foundational studies that have driven our understanding of these processes. We further discuss the recent technological advances that continue to expand our understanding of PDAC complexity. We posit that the clinical translation of these research endeavors will enhance the currently dismal survival rate of this recalcitrant disease.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review surveys how genomic drivers, the tumor microenvironment, metabolism, transcriptional subtypes, and new single-cell/spatial tools have reshaped understanding of pancreatic ductal adenocarcinoma, while noting that clinical gains remain limited. It argues that translating these biological insights into combination and biomarker-guided therapies is needed to improve the poor survival of this disease.
Key findings
- PDAC is the third leading cause of cancer death in the United States and is projected to pass colorectal cancer before 2040; only about 12% of patients are predicted to survive beyond 5 years. Surgery is possible in only 15–20% at diagnosis, and even after resection nearly 3 in 4 patients recur within two years.
- Early detection strongly affects outcome: patients with Stage IA/IB disease had about 80% five-year survival versus less than 10% for advanced disease, but such low-stage cases make up only 3–5% of diagnoses. In a high-risk surveillance trial, almost three-fourths of detected PDAC were Stage I and the same proportion were alive at five years. Neoadjuvant chemoradiation plus adjuvant chemotherapy improved five-year overall survival to 20.5% versus 6.5% with upfront surgery plus adjuvant therapy.
- Genomic drivers are well defined: KRAS mutations occur in over 90% of samples, with KRASG12C in only 1.6% and KRASG12D in more than 40%; germline Fanconi anemia pathway mutations account for 5–7%, and KRAS wild-type alternative drivers for 8–10%. TP53, SMAD4, and CDKN2A loss are common, and CDKN2A/9p21 interferon-cluster loss is linked to an immune-cold environment.
- The TME and metabolism drive resistance: CAFs, extracellular matrix, suppressive myeloid and adaptive immune populations, and metabolic crosstalk involving alanine, lactate, pyrimidines, and other substrates support tumor growth and therapy escape. Transcriptional subtypes have largely coalesced around classical and basal-like states, with the COMPASS trial showing better first-line 5-FU-based responses in classical tumors; single-cell and spatial methods reveal extensive intratumoral heterogeneity.
Methods
- Narrative review; no original patient cohort, clinical trial, or laboratory experiment is reported. It synthesizes published literature, preclinical models, and clinical trial results.
- Thematically organized around treatment paradigms, precursor lesions, genomic drivers, cell-of-origin, transcriptional subtypes, TME, metabolism, new technologies, and clinical trial design.
- Main analysis is qualitative synthesis and interpretation; no systematic search, meta-analysis, or formal risk-of-bias assessment is described.
Limitations
- The paper states that biomarker research is not covered in depth and that cancer vaccines and antibody-drug conjugates are outside its scope.
- Evident from the text: as a narrative review, it does not use a systematic search strategy or formal evidence grading, so selection and interpretation may be selective.
- Evident: many mechanistic and therapeutic claims rely on mouse or preclinical models, and the authors note preclinical models are imperfect and trial translation has often failed; clinical heterogeneity and subtype plasticity further limit generalization.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
222 Not checked yet · 22 Own interpretation · 9 No basis given
In the paper
“patients whose PDAC exhibits a major or complete pathological response to neoadjuvant therapy demonstrate significantly improved overall survival17”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Treatment Strategies for Pancreatic Ductal Adenocarcinoma
What the sources say
- Not checked yetcites [17] Cloyd, 2017, Association of clinical factors with a major pathologic response following preoperative therapy for pancreatic ductal adenocarcinoma, JAMA Surg. source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“nearly 3 in 4 of patients will develop recurrence within two years”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Treatment Strategies for Pancreatic Ductal Adenocarcinoma
What the sources say
- Not checked yetcites [11] Groot, 2018, Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma, Ann. Surg. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“a multitude of circulating tumor-derived analytes (proteins, autoantibodies, metabolites, DNA, non-coding RNAs and extracellular vesicles, among others) have been assessed in the context of PDAC early detection39–41.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Precursor Lesions of Pancreatic Cancer: An Opportunity for Early Detection
What the sources say
- Not checked yetcites [39] Chari, 2015, Early detection of sporadic pancreatic cancer: summative review, Pancreas source
- Not checked yetcites [40] Singhi, 2021, Early detection of pancreatic cancer using DNA-based molecular approaches, Nat. Rev. Gastroenterol. Hepatol. source
- Not checked yetcites [41] Pereira, 2020, Early detection of pancreatic cancer, Lancet Gastroenterol. Hepatol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Approximately 85–90% of PDAC cases are ascribed to originate on the backdrop of PanIN lesions, the remaining 10–15% in cystic precursors20.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Precursor Lesions of Pancreatic Cancer: An Opportunity for Early Detection
What the sources say
- Not checked yetcites [20] Singhi, 2019, Early detection of pancreatic cancer: opportunities and challenges, Gastroenterology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“outside of the minority (10–15%) of cases ascribed to germline mutations or known risk factors, such as mucinous cystic lesions and chronic pancreatitis, there is no single attributable risk factor for most patients4.”
§ Pancreatic Cancer: Advances and Challenges > Introduction:
What the sources say
- Not checked yetcites [4] Petersen, 2016, Familial pancreatic cancer, Semin. Oncol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“More recent IPMN models have been generated that genocopy recurrent driver alterations observed in cognate human lesions (i.e. Kras, Gnas, Rnf43) (Fig 1)34–36, and these models demonstrate the comparable stepwise progression observed in patient derived IPMNs.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Precursor Lesions of Pancreatic Cancer: An Opportunity for Early Detection
What the sources say
- Not checked yetcites [34] Ideno, 2018, GNAS(R201C) induces pancreatic cystic neoplasms in mice that express activated KRAS by inhibiting YAP1 signaling, Gastroenterology source
- Not checked yetcites [35] Patra, 2018, Mutant GNAS drives pancreatic tumourigenesis by inducing PKA-mediated SIK suppression and reprogramming lipid metabolism, Nat. Cell Biol. source
- Not checked yetcites [36] Hosein, 2022, Loss of Rnf43 accelerates kras-mediated neoplasia and remodels the tumor immune microenvironment in pancreatic adenocarcinoma, Gastroenterology source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Mutations in the v-Kiras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are found in over 90% of patient samples45.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [45] 2017, Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma, Cancer Cell source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Recent phylogenetic analyses of precursor lesions from the pancreata of patients with established cancer have confirmed the stepwise progression model and accumulation of genetic alterations in the transition from PanINs to PDAC postulated using more rudimentary techniques26.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Precursor Lesions of Pancreatic Cancer: An Opportunity for Early Detection
What the sources say
- Not checked yetcites [26] Makohon-Moore, 2018, Precancerous neoplastic cells can move through the pancreatic ductal system, Nature source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“suggesting patients undergoing resection also harbor micro-metastatic disease11.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Treatment Strategies for Pancreatic Ductal Adenocarcinoma
What the sources say
- Not checked yetcites [11] Groot, 2018, Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma, Ann. Surg. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“conditional expression of oncogenic mutant Kras in the pancreas, using Cre-recombinase driven by pancreatic transcription factor promoters activated during embryonic development, leads to development of murine PanIN lesions histologically reminiscent of human disease28.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Precursor Lesions of Pancreatic Cancer: An Opportunity for Early Detection
What the sources say
- Not checked yetcites [28] Hingorani, 2003, Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 81
- Probably not a substantial claim. 10
- The quote only partly states this claim. 1
In the paper
“Patients progressing on first-line regimens can be offered the possibility of switching to the other regimen, or a second-line regimen that includes a liposomal formulation of irinotecan in combination with 5-FU10, provided they have not received either of these agents previously.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Treatment Strategies for Pancreatic Ductal Adenocarcinoma
What the sources say
- Not checked yetcites [10] Wang-Gillam, 2016, Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial, Lancet source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“PDAC accounts for greater than 90% of pancreas cancers and has a distinct molecular profile and natural history from pancreatic neuroendocrine tumors”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Precursor Lesions of Pancreatic Cancer: An Opportunity for Early Detection
What the sources say
- Not checked yetcites [22] de Wilde, 2012, Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy, Nat. Rev. Gastroenterol. Hepatol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“almost three-fourths of patients who were diagnosed with PDAC on active surveillance had Stage I disease, and an equal proportion were still alive at five years”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Treatment Strategies for Pancreatic Ductal Adenocarcinoma
What the sources say
- Not checked yetcites [21] Dbouk, 2022, The multicenter cancer of pancreas screening study: impact on stage and survival, J. Clin. Oncol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“two new combination regimens have emerged as the first-line therapy in patients with advanced PDAC. The first is a combination of 5-fluorouracil (5-FU), leucovorin, irinotecan and oxaliplatin, which carries the acronym FOLFIRINOX. The second is the combination of gemcitabine and an albumin nanoparticle conjugate of paclitaxel (nab-paclitaxel)8,9.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Treatment Strategies for Pancreatic Ductal Adenocarcinoma
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“current guidelines advise against screening the general population and instead emphasize biomarker studies be focused on well-defined high-risk cohorts44.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Precursor Lesions of Pancreatic Cancer: An Opportunity for Early Detection
What the sources say
- Not checked yetcites [44] Owens, 2019, Screening for pancreatic cancer: US Preventive Services Task Force reaffirmation recommendation statement, JAMA source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“a remarkable 80% of patients who present with the lowest stages of PDAC (Stage IA or IB disease) were alive at five years, compared to less than 10% of patients with advanced disease19.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Treatment Strategies for Pancreatic Ductal Adenocarcinoma
What the sources say
- Not checked yetcites [19] Blackford, 2020, Recent trends in the incidence and survival of stage 1A pancreatic cancer: A surveillance, epidemiology, and end results analysis, J. Natl. Cancer Inst. source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Patients with Stage IA/IB PDAC are typically diagnosed incidentally and make up no more than 3–5% of cases.
In the paper
“cystic mucinous neoplasms of the pancreas, of which intraductal papillary mucinous neoplasms (IPMNs) are the most common histological subtype, are macroscopic precursors that arise within the main pancreatic duct or one of its branches. These can be observed and followed for progression by imaging techniques25.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Precursor Lesions of Pancreatic Cancer: An Opportunity for Early Detection
What the sources say
- Not checked yetcites [25] Matthaei, 2011, Cystic precursors to invasive pancreatic cancer, Nat. Rev. Gastroenterol. Hepatol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Pancreatic Intraepithelial Neoplasia (PanINs) are the most frequently observed precursor lesions and are, by definition, microscopic lesions that cannot be observed on abdominal imaging scans24.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Precursor Lesions of Pancreatic Cancer: An Opportunity for Early Detection
What the sources say
- Not checked yetcites [24] Overbeek, 2016, Surveillance for neoplasia in the pancreas, Best Pract. Res. Clin. Gastroenterol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“KRAS mutations are observed in most low-grade PanINs and IPMNs, suggesting KRAS is the initiating genetic event driving exocrine neoplasia46,47.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [46] Kanda, 2012, Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia, Gastroenterology source
- Not checked yetcites [47] Fujikura, 2021, Multiregion whole-exome sequencing of intraductal papillary mucinous neoplasms reveals frequent somatic KLF4 mutations predominantly in low-grade regions, Gut source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“deletion of KDM6A results in accelerated tumorigenesis and acquisition of an aggressive transcriptional subtype95–97.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [95] Kalisz, 2020, HNF1A recruits KDM6A to activate differentiated acinar cell programs that suppress pancreatic cancer, EMBO J. source
- Not checked yetcites [96] Yi, 2022, KDM6A regulates cell plasticity and pancreatic cancer progression by noncanonical activin pathway, Cell. Mol. Gastroenterol. Hepatol. source
- Not checked yetcites [97] Andricovich, 2018, Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“altered p53 function has a multitude of tumor-promoting effects on neoplastic cells, including increased genomic instability30, reprogrammed cellular metabolism57,58, and enhanced metastatic propensity59.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [30] Hingorani, 2005, Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice, Cancer Cell source
- Not checked yetcites [57] Morris, 2019, alpha-Ketoglutarate links p53 to cell fate during tumour suppression, Nature source
- Not checked yetcites [58] Rajeshkumar, 2015, Therapeutic targeting of the Warburg effect in pancreatic cancer relies on an absence of p53 function, Cancer Res. source
- Not checked yetcites [59] Weissmueller, 2014, Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor beta signaling, Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a pivotal clinical trial in patients with PDAC and germline BRCA1/2 mutations established the benefit of administering an orally bioavailable PARP inhibitor on improved progression free survival (PFS). This led to the approval of targeted therapy in this setting87.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [87] Golan, 2019, Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, N. Engl. J. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mutations of ATM are the second most frequent known cause of germline mutations in PDAC, after BRCA2, conferring a comparable lifetime increased risk of PDAC in mutation carriers91.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [91] Hsu, 2021, Risk of pancreatic cancer among individuals with pathogenic variants in the ATM gene, JAMA Oncol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the first published clinical series of KRASG12C inhibitor monotherapy in advanced PDAC, responses occurred in a minority of patients (~21%) and were generally transient75.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [75] Strickler, 2023, Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer, N. Engl. J. Med. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Interferon cluster loss creates a “cold” tumor immune milieu and resistance to immunotherapy52”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [52] Barriga, 2022, Machete identifies interferon-encompassing chromosome 9p21.3 deletions as mediators of immune evasion and metastasis, Nat. Cancer source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: CDKN2A is often lost by homozygous deletions at chromosome 9p21, which is associated with codeletions of a neighboring interferon cluster in half of cases.
In the paper
“the KRASG12C allele occurs in only 1.6% of PDAC cases, whereas the KRASG12D allele is present in greater than 40%, followed in frequency by KRASG12V and KRASG12R mutations74.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [74] Waters, 2018, KRAS: the critical driver and therapeutic target for pancreatic cancer, Cold Spring Harb. Perspect. Med. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Chromatin remodeling and SWI/SNF complex genes are one of the most frequently altered class of genes in PDAC45,48–50, and can occur via somatic deletions of the associated chromosomal loci94.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Genomic Drivers of Pancreatic Cancer
What the sources say
- Not checked yetcites [45] 2017, Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma, Cancer Cell source
- Not checked yetcites [48] Jones, 2008, Core signaling pathways in human pancreatic cancers revealed by global genomic analyses, Science source
- Not checked yetcites [49] Waddell, 2015, Whole genomes redefine the mutational landscape of pancreatic cancer, Nature source
- Not checked yetcites [50] Bailey, 2016, Genomic analyses identify molecular subtypes of pancreatic cancer, Nature source
- Not checked yetcites [94] Shain, 2012, Convergent structural alterations define SWItch/Sucrose nonfermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer, Proc. Natl. Acad. Sci. USA source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mauer et al., found isolated epithelial tissues supported the Moffitt “classical” or “basal-like” subtypes, while they found no evidence of the Bailey “ADEX” subtype or Collisson “exocrine-like” subtypes in epithelial enriched tumor samples132.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Transcriptional Subtypes of Human Pancreatic Cancer
What the sources say
- Not checked yetcites [132] Maurer, 2019, Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes, Gut source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“these subtypes could predict drug response in cell culture models, and patient outcomes were significantly different across their subtypes.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Transcriptional Subtypes of Human Pancreatic Cancer
What the sources say
- Not checked yetcites [130] Collisson, 2011, Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy, Nat. Med. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Deletion of the ductal progenitor gene Sox9 prevented KRAS-driven transformation, while Sox9 overexpression accelerated PanIN development.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Cell-of-Origin: An Unsettled Debate
What the sources say
- Not checked yetcites [118] Kopp, 2012, Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“samples “ADEX” or “exocrine-like” signatures are associated with low PDAC cellularity45, suggesting these signals derive from stromal/immune/non-cancerous elements of tissues.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Transcriptional Subtypes of Human Pancreatic Cancer
What the sources say
- Not checked yetcites [45] 2017, Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma, Cancer Cell source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moffit and colleagues devised a “virtual dissection strategy” to computationally subtract the transcriptional background imposed by stromal and immune cells from bulk-RNA sequencing signatures131. Using this approach, they identified two subtypes of PDAC tumors, termed “classical” and “basal-like”, in addition to two stromal subtypes termed “normal stroma” and “activated stroma”.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Transcriptional Subtypes of Human Pancreatic Cancer
What the sources say
- Not checked yetcites [131] Moffitt, 2015, Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma, Nat. Genet. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“they suggested that their findings demonstrate that the Bailey ADEX subtype is likely contamination of pancreatic acinar cells.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Transcriptional Subtypes of Human Pancreatic Cancer
What the sources say
- Not checked yetcites [133] Puleo, 2018, Stratification of pancreatic ductal adenocarcinomas based on tumor and microenvironment features, Gastroenterology source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“consensus has best coalesced around two major subtypes, classical and basal-like, with some populations showing mixed features135”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Transcriptional Subtypes of Human Pancreatic Cancer
What the sources say
- Not checked yetcites [135] Collisson, 2019, Molecular subtypes of pancreatic cancer, Nat. Rev. Gastroenterol. Hepatol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Fibroblasts represent the most abundant cell type in the TME and are largely responsible for the deposition of the extracellular matrix driving the characteristic physiological properties of PDAC140”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [140] Provenzano, 2012, Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“several candidate regulators such as TP63136, which can be induced by KDM6A loss97, can promote more aggressive subtypes”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Transcriptional Subtypes of Human Pancreatic Cancer
What the sources say
- Not checked yetcites [136] Somerville, 2018, TP63-mediated enhancer reprogramming drives the squamous subtype of pancreatic ductal adenocarcinoma, Cell Rep. source
- Not checked yetcites [97] Andricovich, 2018, Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“They identified five different subtypes of PDAC tumors: “basal-like-A”, “basal-like-B”, “hybrid”, “classical-A” and “classical-B”.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Transcriptional Subtypes of Human Pancreatic Cancer
What the sources say
- Not checked yetcites [134] Chan-Seng-Yue, 2020, Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution, Nat. Genet. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“They reported best overlap with the Moffitt subtypes, and their resolution allowed for subclassification of both, while their hybrid subtype did not consistently fall into previously reported classes.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Transcriptional Subtypes of Human Pancreatic Cancer
What the sources say
- Not checked yetcites [134] Chan-Seng-Yue, 2020, Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution, Nat. Genet. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the transcriptional profiles of apCAFs overlap with mesothelial cells150, and based on lineage tracing studies in mice have been postulated to derive from a mesothelial origin145”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [150] Feig, 2013, Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer, Proc. Natl. Acad. Sci. USA source
- Not checked yetcites [145] Han, 2023, The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis, Nat. Commun. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CD40 agonists to reprogram macrophages to a less immunosuppressive status, leading to CD8 T cell infiltration that would drive the conversion from a “cold” to a “hot tumor”183”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [183] Padrón, 2022, Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial, Nat. Med. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“targeting MDSCs and/or TAMs improves adaptive immune responses in mouse models of pancreatic cancer and can potentiate checkpoint inhibition approaches176,177,179,180”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [176] Pylayeva-Gupta, 2012, Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia, Cancer Cell source
- Not checked yetcites [177] Zhu, 2017, Tissue-resident macrophages in pancreatic ductal adenocarcinoma originate from embryonic hematopoiesis and promote tumor progression, Immunity source
- Not checked yetcites [179] Candido, 2018, CSF1R(+) macrophages sustain pancreatic tumor growth through T cell suppression and maintenance of key gene programs that define the squamous subtype, Cell Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Depletion of these fibroblasts, or targeting of CXCL12, sensitizes PDAC to immune checkpoint blockade in preclinical models151”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [151] Hutton, 2021, Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the specific nature of the sub-TME in an individual tumor did not predict outcome, but higher sub-TME heterogeneity was a poor prognostic sign”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“PDAC cells produce “tonic” (low) levels of a distinct oncogenic homo-trimeric collagen that binds to α3β1 integrin, thereby mediating immune suppression and reprogramming the tumor-associated microbiome167”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [167] Aguilera, 2017, Inhibition of discoidin domain Receptor 1 reduces collagen-mediated tumorigenicity in pancreatic ductal adenocarcinoma, Mol. Cancer Ther. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Focal adhesion kinase (FAK), hyperactivated in pancreatic cancer cells, is an important driver of fibrosis and immune suppression in the TME174”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [174] Lander, 2022, Stromal reprogramming by FAK inhibition overcomes radiation resistance to allow for immune priming and response to checkpoint blockade, Cancer Discov. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“FAK inhibition was shown to markedly reduced fibrosis and decreased the infiltration of tumor-promoting immune cells in mice.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CAFs expressing Fibroblast Activation Protein (FAP) also express high levels of CXCL12 and inhibit tumor T cell infiltration.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [151] Hutton, 2021, Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Dendritic cells (DCs) are found in low numbers in PDAC, as compared to other tumor types, and the DCs present are of poor quality for antigen presentation186”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [186] Byrne, 2016, CD40 stimulation obviates innate sensors and drives T cell immunity in cancer, Cell Rep. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The majority of collagen is type I collagen164, largely generated by CAFs147,165”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [164] Hosein, 2020, Pancreatic cancer stroma: an update on therapeutic targeting strategies, Nat. Rev. Gastroenterol. Hepatol. source
- Not checked yetcites [147] Biffi, 2019, IL1-induced JAK/STAT signaling is antagonized by TGFbeta to shape CAF heterogeneity in pancreatic ductal adenocarcinoma, Cancer Discov. source
- Not checked yetcites [165] Chen, 2021, Type I collagen deletion in alphaSMA(+) myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Oncogenic KRAS signaling drives expression of granulocyte colony stimulating factor (GM-CSF) by PDAC cells, promoting recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs)176,177”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [176] Pylayeva-Gupta, 2012, Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia, Cancer Cell source
- Not checked yetcites [177] Zhu, 2017, Tissue-resident macrophages in pancreatic ductal adenocarcinoma originate from embryonic hematopoiesis and promote tumor progression, Immunity source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Hyaluronic acid is a glycosaminoglycan polymer, thought to be released by predominantly by CAFs, that avidly retains water and promotes the characteristically high interstitial fluid pressure found in pancreatic tumors140”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [140] Provenzano, 2012, Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma, Cancer Cell source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Targeted deletion of type I collagen from SMA-expressing fibroblasts increases immune suppressive myeloid infiltration, accelerating tumor progression166”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [166] Chen, 2022, Oncogenic collagen I homotrimers from cancer cells bind to alpha3beta1 integrin and impact tumor microbiome and immunity to promote pancreatic cancer, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“MyCAFs are localized close to the neoplastic cells and thought to be responsible for deposition of extracellular matrix, whereas iCAFs tend to occupy spaces between islands of the PDAC cells and release IL6 and other anti-inflammatory cytokines.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [147] Biffi, 2019, IL1-induced JAK/STAT signaling is antagonized by TGFbeta to shape CAF heterogeneity in pancreatic ductal adenocarcinoma, Cancer Discov. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Early efforts to identify and understand different CAF populations identified a myofibroblast-like population (myCAF) and an inflammatory fibroblast population (iCAF)147”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [147] Biffi, 2019, IL1-induced JAK/STAT signaling is antagonized by TGFbeta to shape CAF heterogeneity in pancreatic ductal adenocarcinoma, Cancer Discov. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“CAFs are largely responsible for deposition of the dense extracellular matrix found in PDAC, largely consisting of collagen and hyaluronic acid.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [140] Provenzano, 2012, Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“novel agonists developed in PDAC models to target the CD11b/CD18 receptor present on most tumor-infiltrating myeloid subsets have shown promising pre-clinical data, currently being tested in the clinic181,182”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“fibroblasts expressing leucine-rich-repeat-containing protein 15 (LRRC15) were identified in mouse PDAC but not in the normal pancreas, and these fibroblasts are postulated to promote tumor growth and inhibit anti-tumor immune responses153”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [153] Shaashua, 2022, BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling, Nat. Commun. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“FAK inhibition-mediated reprogramming of the stroma was shown to overcome radiation resistance and sensitize the tumors to immunotherapy175”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [175] Bayne, 2012, Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer, Cancer Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Examples include the non-oxidative pentose phosphate pathway, which enables nucleotide biosynthesis, and the hexosamine biosynthesis pathway, which generates GlcNAc required for posttranslational modifications64,195”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Combined pharmacological targeting of MEK or ERK with hydroxychloroquine potently inhibits xenograft tumor growth and has shown efficacy in clinical treatment of PDAC, with additional trials on-going.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“increased biogenesis of lysosomes and constitutive engagement of the autophagy “self-eating” recycling program206”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [206] Yang, 2011, Pancreatic cancers require autophagy for tumor growth, Genes Dev. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Increased expression of NCOA4 accelerates tumorigenesis in mice, and genetic ablation leads to delayed tumor growth that is eventually overcome through development of compensatory iron acquisition pathways216”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [216] Ravichandran, 2022, Coordinated transcriptional and catabolic programs support iron-dependent adaptation to RAS-MAPK pathway inhibition in pancreatic cancer, Cancer Discov. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Oncogenic Ras also drives glutamine anaplerosis to provide a significant source of carbon for TCA cycle, biosynthesis of glutathione necessary to detoxify reactive oxygen species (ROS), and enables a non-canonical malate-aspartate shuttle to generate NADPH for redox balance198”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [198] Biancur, 2017, Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism, Nat. Commun. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“6-Diazo-5-oxo-l-norleucine (DON) was identified as a potential anti-cancer glutamine antagonist more than a half century ago201, but its lack of substrate specificity provided too much off-target toxicity202.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [201] Lynch, 1982, Phase II evaluation of DON (6-diazo-5-oxo-L-norleucine) in patients with advanced colorectal carcinoma, Am. J. Clin. Oncol. source
- Not checked yetcites [202] Rais, 2016, Discovery of 6-Diazo-5-oxo-l-norleucine (DON) prodrugs with enhanced CSF delivery in monkeys: A potential treatment for glioblastoma, J. Med. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“recent advances have optimized DON as a pro-drug with pharmacokinetic properties that increase tumor targeting203, including an orally available analog with promising pre-clinical results in murine PDAC models204”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [203] Leone, 2019, Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion, Science source
- Not checked yetcites [204] Sharma, 2020, Targeting tumor-intrinsic hexosamine biosynthesis sensitizes pancreatic cancer to anti-PD1 therapy, J. Clin. Invest. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“MEK-inhibition in PDAC increased both lysosome biosynthesis and ferritinophagy, necessary to support increased iron-sulfur cluster proteins for respiration217”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [217] Dixon, 2012, Ferroptosis: an iron-dependent form of nonapoptotic cell death, Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“MHC-I expression is low at the PDAC cell surface, instead found predominantly localized within autophagosomes and lysosomes227”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [227] Zhu, 2021, Functional genomics in vivo reveal metabolic dependencies of pancreatic cancer cells, Cell Metab. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Labile iron can also potentiate cell death via the lipid oxidation process known as “ferroptosis”218”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [218] Badgley, 2020, Cysteine depletion induces pancreatic tumor ferroptosis in mice, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“ferritin is trafficked to autophagosomes via nuclear receptor coactivator 4 (NCOA4), and free iron is subsequently released by autophagy through a process termed “ferritinophagy”214”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [214] Pantopoulos, 2012, Mechanisms of mammalian iron homeostasis, Biochemistry source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mutant KRAS drives upregulated glycolysis, not only increasing production of lactate, but also providing key carbon inputs for synthesis of molecules required for proliferation.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This shift in immune infiltration follows a loss of myCAFs upon Treg depletion, as Tregs proved a significant source of TGF-beta.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
What the sources say
- Not checked yetcites [192] Kamphorst, 2015, Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein, Cancer Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Differential activation of the integrated stress response can also be used to define sub-populations within individual tumors, which drives differential sensitivity to metabolic inhibitors239.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Metabolic Heterogeneity in Pancreatic Cancer
What the sources say
- Not checked yetcites [239] Recouvreux, 2020, Glutamine depletion regulates Slug to promote EMT and metastasis in pancreatic cancer, J. Exp. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“High glycolytic flux is required to maintain upregulated PGD metabolism, and this in maintained in part through suppression of thioredoxin-interacting protein (TXNIP) transcription243.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Metabolic Heterogeneity in Pancreatic Cancer
What the sources say
- Not checked yetcites [243] Sancho, 2015, MYC/PGC-1alpha balance determines the metabolic phenotype and plasticity of pancreatic cancer stem cells, Cell Metab. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“only a subset of PDAC cell lines with mutant KRAS demonstrate a constitutive macropinocytosis program, whereas others engage this process only when challenged with glutamine deprivation235”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
What the sources say
- Not checked yetcites [235] Yamamoto, 2020, Molecular imaging of the tumor microenvironment reveals the relationship between tumor oxygenation, glucose uptake, and glycolysis in pancreatic ductal adenocarcinoma, Cancer Res. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the metabolic milieu in pancreatic tumors is deregulated, with some nutrients being enriched and others depleted.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Metabolic Heterogeneity in Pancreatic Cancer
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The glycolytic metabolic subtype aligns with a “quasimesenchymal” transcriptional subtype and lipogenic metabolism state with a “classical” signature130.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Metabolic Heterogeneity in Pancreatic Cancer
What the sources say
- Not checked yetcites [130] Collisson, 2011, Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy, Nat. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“the deoxycytidine released among these pyrimidines inhibits the efficacy of the standard of care chemotherapy gemcitabine, and depletion of myeloid cells in mice sensitizes PDAC tumors to gemcitabine treatment.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Metabolic Interactions in the Pancreatic Tumor Immune Microenvironment
What the sources say
- Not checked yetcites [258] Dalin, 2019, Deoxycytidine release from pancreatic stellate cells promotes gemcitabine resistance, Cancer Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These combine to enable PDAC cells to survive nutrient challenging conditions in the primary tumor and provide metabolic flexibility to enable metastasis.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Pancreatic Cancer Metabolism: Adaptations Present Therapeutic Opportunities
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“metabolic inhibition approaches combined with RAS pathway inhibitors have shown strong pre-clinical data and are currently in clinical trials197,224,225”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Metabolic Heterogeneity in Pancreatic Cancer
What the sources say
- Not checked yetcites [197] Son, 2013, Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway, Nature source
- Not checked yetcites [224] Kinsey, 2019, Protective autophagy elicited by RAF-->MEK-->ERK inhibition suggests a treatment strategy for RAS-driven cancers, Nat. Med. source
- Not checked yetcites [225] Garrido, 2016, The urgent need to recover MHC class I in cancers for effective immunotherapy, Curr. Opin. Immunol. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Further, patient-derived organoid transcriptional landscape and sub-population proportions shift during passaging137,271”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > New Technologies Driving New Insights
What the sources say
- Not checked yetcites [137] Raghavan, 2021, Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer, Cell source
- Not checked yetcites [271] Schalck, 2022, Single-cell sequencing reveals trajectory of tumor-infiltrating lymphocyte states in pancreatic cancer, Cancer Discov. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, addition of contextual factors lacking in such ex vivo culture models can potentially rescue the heterogeneity of the original tumor models and the retain the ability to predict response to therapy137.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > New Technologies Driving New Insights
What the sources say
- Not checked yetcites [137] Raghavan, 2021, Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer, Cell source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“scRNA-seq data confirmed the existence of multiple CAF populations within human and murine pancreatic tumors and allowed the discovery of apCAFs149.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > New Technologies Driving New Insights
What the sources say
- Not checked yetcites [149] Dominguez, 2020, Single-cell RNA sequencing reveals stromal evolution into LRRC15(+) myofibroblasts as a determinant of patient response to cancer immunotherapy, Cancer Discov. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, our increased understanding of the symbiotic support mechanisms of nutrients within the pancreatic TME have already identified several therapeutic opportunities.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Metabolic Interactions in the Pancreatic Tumor Immune Microenvironment
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Neural invasion is a well-recognized feature of pancreatic tumors, with the severity negatively correlating to prognosis262.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Metabolic Interactions in the Pancreatic Tumor Immune Microenvironment
What the sources say
- Not checked yetcites [262] Banh, 2020, Neurons release serine to support mRNA translation in pancreatic cancer, Cell source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increased understanding of the biology of PDAC has led to a plethora of clinical trials to improve treatment; however, most have fallen short of expectations.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Clinical Trials: Setting Expectations for Future Success
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Among common solid cancers, PDAC is among the most frequent to fail Phase 3 trials.
In the paper
“These further identified that CD8 T cells show indications of systemic exhaustion, and a network analysis of potential checkpoint receptor-ligand pairing suggested TIGIT as a key node of immune-suppression.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > New Technologies Driving New Insights
What the sources say
- Not checked yetcites [277] Freed-Pastor, 2021, The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer, Cancer Cell source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Integration of multiple scRNA-seq datasets combined with lineage tracing studies demonstrated that ap-CAFs can arise from a mesothelial origin and regulate the expansion of regulatory T cells and immune suppression145.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > New Technologies Driving New Insights
What the sources say
- Not checked yetcites [145] Han, 2023, The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis, Nat. Commun. source
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This has the dual benefit of tumor shrinkage and acts as an in situ antigen release mechanism to allow for an immune response.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Clinical Trials: Setting Expectations for Future Success
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This has led to calls to revamp how drug development is furthered for this disease, and to redefine the thresholds needed for agents to move forward to larger phase trials281,282.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Clinical Trials: Setting Expectations for Future Success
What the sources say
- Not checked yetcites [281] Thota, 2017, Preclinical rationale for the Phase III trials in metastatic pancreatic cancer: is wishful thinking clouding successful drug development for pancreatic cancer?, Pancreas source
- Not checked yetcites [282] O'Reilly, 2019, Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: A Phase 2 randomized clinical trial, JAMA Oncol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: Among common solid cancers, PDAC is among the most frequent to fail Phase 3 trials.
In the paper
“Similarly, the combined use of spatial profiling with single-nucleus RNA sequencing has enabled the interrogation of the response of PDAC to neoadjuvant therapy and identified a treatment-refractory “neural-like” progenitor cell type that escapes standard of care regimens279.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > New Technologies Driving New Insights
What the sources say
- Not checked yetcites [279] He, 2022, High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging, Nat. Biotechnol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Of note, while many differences in immune infiltration and behavior were found between different patients, this ability to spatially assess these data allowed the observation of widespread heterogeneity in individual patients.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > New Technologies Driving New Insights
What the sources say
- Not checked yetcites [275] Kiemen, 2022, CODA: quantitative 3D reconstruction of large tissues at cellular resolution, Nat. Methods source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these studies demonstrate that targeting metabolism is not as simple as defining metabolic vulnerabilities of the cancer cells, and the metabolic state of PDAC cells is heterogenous within individual tumors.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Metabolic Interactions in the Pancreatic Tumor Immune Microenvironment
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a recent preclinical study, dual therapy against CD8 T cell checkpoints using a 41-BB agonist and LAG-3 inhibitor by itself was ineffectual, and yet when administered with a myeloid cell targeted CXCR1/2 antagonist, the triple regimen led to sustained responses in biologically relevant models285.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Clinical Trials: Setting Expectations for Future Success
What the sources say
- Not checked yetcites [285] O'Hara, 2021, CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study, Lancet Oncol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Subsequently, attempts to inactivate CAFs through sonic hedgehog inhibition proved ineffective in patients289, and preclinical studies that were conducted after the fact pinpointed reasons for this failure159,290.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Clinical Trials: Setting Expectations for Future Success
What the sources say
- Not checked yetcites [289] Özdemir, 2015, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Cancer Cell source
- Not checked yetcites [159] Özdemir, 2014, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Cancer Cell source
- Not checked yetcites [290] Hingorani, 2023, Epithelial and stromal co-evolution and complicity in pancreatic cancer, Nat. Rev. Cancer source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“One notable example of an ultimately unsuccessful but informative clinical paradigm came by way of a series of pre-clinical studies proposing the efficacy of systemic therapy would improve through efforts to penetrate the dense fibrosis and high interstitial pressure promoted by the CAFs in pancreatic tumors140,158.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Clinical Trials: Setting Expectations for Future Success
What the sources say
- Not checked yetcites [140] Provenzano, 2012, Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma, Cancer Cell source
- Not checked yetcites [158] Rhim, 2014, Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma, Cancer Cell source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Significant progress has been made in understanding the biology of pancreatic cancer over the past several decades, unfortunately, these have not translated into a breakthrough in clinical care for the majority of patients.”
§ Pancreatic Cancer: Advances and Challenges > Summary:
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Among common solid cancers, PDAC is among the most frequent to fail Phase 3 trials.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While preclinical models remain far from perfect, they do offer valuable insights into potential mechanisms of failure when trials are unsuccessful.”
§ Pancreatic Cancer: Advances and Challenges > Introduction: > Clinical Trials: Setting Expectations for Future Success
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Patients with Stage IA/IB PDAC are typically diagnosed incidentally and make up no more than 3–5% of cases.
“patients with such low stage tumors are typically diagnosed incidentally and comprise no more than 3–5% of cases.”
The paper relies on this without support.
CA19-9 is the most widely used diagnostic biomarker for PDAC but has suboptimal sensitivity in early-stage disease.
“The carbohydrate antigen 19–9 (CA19–9), also known as sialyl-Lewisa, is currently the most widely used diagnostic biomarker for PDAC, although it has a suboptimal sensitivity in early-stage disease.”
The paper relies on this without support.
CDKN2A is often lost by homozygous deletions at chromosome 9p21, which is associated with codeletions of a neighboring interferon cluster in half of cases.
“CDKN2A is often lost by homozygous deletions at the chromosomal 9p21 locus, which is associated with codeletions of a neighboring interferon cluster in half of cases.”
The paper relies on this without support.
Neoplastic cells in PDAC often constitute a minority of the overall cellularity within the tumor.
“The neoplastic cells in PDAC often constitute a minority of the overall cellularity within the tumor.”
The paper relies on this without support.
The aggressive biology, therapy resistance, and heterogeneity of PDAC are driven nearly as much by non-cancerous tumor components as by PDAC cells.
“Indeed, the aggressive biology, resistance to therapy, and heterogeneity of the disease is driven nearly as much by the non-cancerous components of the tumor as the PDAC cells.”
The paper relies on this without support.
Myeloid cell populations make up the largest immune cell population in pancreatic tumors.
“Myeloid cell populations make up the largest immune cell population in pancreatic tumors (Fig. 3).”
The paper relies on this without support.
A lack of infiltration by cytotoxic CD8 T cells is a notable feature of the PDAC tumor microenvironment.
“One of the most notable features of the PDAC TME is the lack of infiltration by cytotoxic CD8 T cells.”
The paper relies on this without support.
Physical barriers in PDAC tumors limit access to blood-derived nutrients and oxygen, leading to dysregulated nutrient profiles and regional hypoxia.
“The physical barriers imposed within PDAC tumors function to limit access to blood-derived nutrients and oxygen, leading to dysregulate nutrient profiles and promote regional hypoxia.”
The paper relies on this without support.
PDAC cells exhibit numerous adaptations that allow them to survive and thrive under the nutrient constraints imposed by the tumor microenvironment.
“PDAC cells exhibit numerous adaptations to not only survive but thrive under the nutrient constraints imposed by the TME.”
The paper relies on this without support.
Neoplastic epithelial cells within PDAC tumors are often vastly outnumbered by stromal and immune cell populations.
“the neoplastic epithelial cells within PDAC tumors are often vastly outnumbered by the stromal and immune cell populations.”
The paper relies on this without support.
The varied localization, motility, and function of stromal and immune cell populations translate to differential nutrient requirements and can lead to tumor-supporting metabolic interactions.
“The varied localization, motility, and function of these different cell populations translate to differential nutrient requirements and can lead to tumor-supporting metabolic interactions.”
The paper relies on this without support.
These symbiotic metabolic interactions fuel PDAC metabolism, promote resistance to chemotherapy, and drive mechanisms of immune suppression.
“These symbiotic interactions fuel PDAC metabolism, promote resistance to chemotherapy, and drive mechanisms of immune suppression (Figure 4b).”
The paper relies on this without support.
Among common solid cancers, PDAC is among the most frequent to fail Phase 3 trials.
“In fact, PDAC suffers from one of the highest rates of Phase 3 failures amongst common solid cancers.”
The paper relies on this without support.
A treatment's clinical success depends critically on the underlying tumor biology.
“The indelible lessons we continue to learn are that the past is prologue and that the underlying biology remains one of the most pivotal arbitrators of meaningful success in the clinic.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Clinical care for these patients is through systemic chemotherapy, with the first lines of therapy being gemcitabine (GEM), GEM plus nab‐paclitaxel or FOLFIRINOX [5].”
From Pyrvinium Pamoate Alone and With Gemcitabine Exhibits Anti‐Pancreatic Cancer Activity in 2D and 3D Cell Culture Models (2024) · cites this paper as [5]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“three in four PDAC patients develop recurrence within 2 years after resection”
From Pyrvinium Pamoate Alone and With Gemcitabine Exhibits Anti‐Pancreatic Cancer Activity in 2D and 3D Cell Culture Models (2024) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“suggesting that even the small proportion of patients who undergo surgical resection harbour micro‐metastasis [5]”
From Pyrvinium Pamoate Alone and With Gemcitabine Exhibits Anti‐Pancreatic Cancer Activity in 2D and 3D Cell Culture Models (2024) · cites this paper as [5]
In the citing paper
“Context-specific tumor suppressive or oncogenic functions of SWI/SNF chromatin regulation was noticed in PDAC64,65.”
From Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma (2024) · cites this paper as [64]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Pancreatic Cancer: Advances and Challenges > Introduction: > The Pancreatic Cancer Tumor Microenvironment
“Oncogenic KRAS signaling drives expression of granulocyte colony stimulating factor (GM-CSF) by PDAC cells, promoting recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs)176,177.”
§ Pancreatic Cancer: Advances and Challenges > References
“Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer.”
Citations
Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691
Siegel, R. L., Miller, K. D., Wagle, N. S., & Jemal, A. (2023) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21763 · Cited by 16,303
Jemal, A., Siegel, R., Xu, J., & Ward, E. (2010) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20073 · Cited by 12,596
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Conroy, T., Desseigne, F., Ychou, M., Bouché, O., Guimbaud, R., Bécouarn, Y., Adenis, A., Raoul, J.-L., Gourgou-Bourgade, S., de la Fouchardière, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011923 · Cited by 7,810
Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M., & Matrisian, L. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0155 · Cited by 7,094
Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine
Von Hoff, D. D., Ervin, T., Arena, F. P., Chiorean, E. G., Infante, J., Moore, M., Seay, T., Tjulandin, S. A., Ma, W. W., Saleh, M. N., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1304369 · Cited by 6,712
Trastuzumab-Induced Hepatotoxicity: A Case Report
Vucicevic, D., Carey, E. J., & Karlin, N. J. (2013) · Breast Care · doi:10.1159/000346844 · Cited by 4,432
Brocken, P., van der Heijden, E. H. F. M., Dekhuijzen, P. N. R., Peters-Bax, L., & de Geus‐Oei, L. (2013) · Respiration · doi:10.1159/000347096 · Cited by 4,011
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969
Self-citation
Cited by
Sorted by citations
Liquid biopsy in cancer: current status, challenges and future prospects
Ma, L., Guo, H., Zhao, Y., Liu, Z., Wang, C., Bu, J., Sun, T., & Wei, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02021-w · Cited by 820
Lactate and lactylation in cancer
Chen, J., Huang, Z., Chen, Y., Tian, H., Chai, P., Shen, Y., Yao, Y., Xu, S., Ge, S., & Jia, R. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02082-x · Cited by 545
Li, F., Si, W., Xia, L., Yin, D., Wei, T., Tao, M., Cui, X., Yang, J. P., Hong, T., & Wei, R. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02008-9 · Cited by 403
IL-1β+ macrophages fuel pathogenic inflammation in pancreatic cancer
Caronni, N., Terza, F. L., Vittoria, F. M., Barbiera, G., Mezzanzanica, L., Cuzzola, V., Barresi, S., Pellegatta, M., Canevazzi, P., Dunsmore, G., et al. (2023) · Nature · doi:10.1038/s41586-023-06685-2 · Cited by 418
A Small Molecule with Big Impact: MRTX1133 Targets the KRASG12D Mutation in Pancreatic Cancer
Wei, D., Wang, L., Zuo, X., Maitra, A., & Bresalier, R. S. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-2098 · Cited by 177
Self-citationTargeting pancreatic cancer metabolic dependencies through glutamine antagonism
Encarnación-Rosado, J., Sohn, A. S. W., Biancur, D. E., Lin, E. Y., Osorio-Vasquez, V., Rodrick, T. C., González-Baerga, D., Zhao, E., Yokoyama, Y., Simeone, D. M., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00647-3 · Cited by 138
Cregg, J., Edwards, A. V., Chang, S., Lee, B. J., Knox, J. E., Tomlinson, A. C. A., Marquez, A., Liu, Y., Freilich, R., Aay, N., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02314 · Cited by 128
Spatial mapping of transcriptomic plasticity in metastatic pancreatic cancer
Pei, G., Min, J., Rajapakshe, K., Branchi, V., Liu, Y., Selvanesan, B. C., Thege, F. I., Sadeghian, D., Zhang, D., Cho, K. S., et al. (2025) · Nature · doi:10.1038/s41586-025-08927-x · Cited by 121
Self-citationFrontiers in pancreatic cancer on biomarkers, microenvironment, and immunotherapy
Yu, B., Shao, S., & Ma, W. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217350 · Cited by 119
Assouline, B., Kahn, R., Hodali, L., Condiotti, R., Engel, Y., Elyada, E., Mordechay‐Heyn, T., Pitarresi, J. R., Atias, D., Steinberg, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50441-7 · Cited by 105
Shiau, C., Cao, J., Gong, D. H., Gregory, M., Caldwell, N. J., Yin, X., Cho, J.-W., Wang, P. L., Su, J., Wang, S., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01890-9 · Cited by 103
Leiphrakpam, P. D., Chowdhury, S., Zhang, M. H., Bajaj, V., Dhir, M., & Are, C. (2025) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-025-01183-2 · Cited by 99
Li, T., Hu, C., Huang, T., Zhou, Y., Tian, Q., Chen, H., He, R., Yuan, Y., Yong, J., Jiang, H., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-24-3173 · Cited by 94
Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma
Yousef, A., Yousef, M., Chowdhury, S., Abdilleh, K., Knafl, M., Edelkamp, P., Alfaro-Munoz, K., Chacko, R., Peterson, J., Smaglo, B. G., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00505-0 · Cited by 93
Self-citationEmerging mechanisms and promising approaches in pancreatic cancer metabolism
Wu, H., Fu, M., Wu, M., Cao, Z., Zhang, Q., & Liu, Z. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06930-0 · Cited by 97
Yang, J., Yu, X., Xiao, M., He, X., Tan, Z., Lei, Y., Guo, Y., Wang, W., Xu, J., Shi, S., et al. (2025) · Gut · doi:10.1136/gutjnl-2024-334361 · Cited by 103
Chiaro, P. D., Nacci, L., Arco, F., Brandini, S., Polletti, S., Palamidessi, A., Donati, B., Soriani, C., Gualdrini, F., Frigè, G., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.02.017 · Cited by 80
Macrophages and fibroblasts as regulators of the immune response in pancreatic cancer
Shakiba, M., & Tuveson, D. A. (2025) · Nature Immunology · doi:10.1038/s41590-025-02134-6 · Cited by 81
Targeting PIKfyve-driven lipid metabolism in pancreatic cancer
Cheng, C., Hu, J., Mannan, R., He, T., Bhattacharyya, R., Magnuson, B., Wisniewski, J. P., Peters, S., Karim, S. A., MacLean, D., et al. (2025) · Nature · doi:10.1038/s41586-025-08917-z · Cited by 79
Self-citationYin, N., Li, X., Zhang, X., Xue, S., Cao, Y., Niedermann, G., Lu, Y., & Xue, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01826-z · Cited by 74
Wang, B., Deng, J., Donati, V. L., Merali, N., Frampton, A. E., Giovannetti, E., & Deng, D. (2024) · Pathogens · doi:10.3390/pathogens13010093 · Cited by 73
From Machine Learning to Patient Outcomes: A Comprehensive Review of AI in Pancreatic Cancer
Tripathi, S., Tabari, A., Mansur, A., Dabbara, H., Bridge, C. P., & Daye, D. (2024) · Diagnostics · doi:10.3390/diagnostics14020174 · Cited by 70
Donahue, K. L., Watkoske, H. R., Kadiyala, P., Du, W., Brown, K. L., Scales, M. K., Elhossiny, A. M., Espinoza, C. E., Opsahl, E. L. L., Griffith, B. D., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0100 · Cited by 60
Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity
Xu, Y., Wang, X., Li, Y., Mao, Y., Su, Y., Mao, Y., Yang, Y., Gao, W., Fu, C., Chen, W., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54438-0 · Cited by 68
Loveless, I. M., Kemp, S. B., Hartway, K. M., Mitchell, J. T., Wu, Y., Zwernik, S. D., Salas-Escabillas, D. J., Brender, S. M., George, M., Makinwa, Y., et al. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-2183 · Cited by 59
Xu, L., Xie, Y., Lin, J., Wu, A., & Jiang, T. (2023) · Open Research (University of Surrey) · doi:10.1002/viw.20230070 · Cited by 55
NFE2L2 and SLC25A39 drive cuproptosis resistance through GSH metabolism
Liu, J., Tang, H., Chen, F., Li, C., Xie, Y., Kang, R., & Tang, D. (2024) · Scientific Reports · doi:10.1038/s41598-024-81317-x · Cited by 63
Jiang, S., Ma, W., Ma, C., Zhang, Z., Zhang, W., & Zhang, J. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2341717 · Cited by 52
Acidosis orchestrates adaptations of energy metabolism in tumors
Groessl, S., Kalis, R., Snaebjornsson, M. T., Wambach, L., Haider, J., Andersch, F., Schulze, A., Palm, W., & Zuber, J. A. (2025) · Science · doi:10.1126/science.adp7603 · Cited by 58
Zheng, S., Tian, Q., Yuan, Y., Sun, S., Li, T., Xia, R., He, R., Luo, Y., Lin, Q., Fu, Z., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02854-3 · Cited by 50
Mukund, A., Afridi, M. A., Karolak, A. M., Park, M. A., Permuth, J. B., & Rasool, G. (2024) · Cancers · doi:10.3390/cancers16122240 · Cited by 59
The immunometabolic ecosystem in cancer
Bantug, G. R., & Hess, C. (2023) · Nature Immunology · doi:10.1038/s41590-023-01675-y · Cited by 53
Melle, F., Menon, D., Conniot, J., Ostolaza-Paraiso, J., Argandona, S. M., Oliveira, J., Chen, X., Mendes, B. B., Conde, J., & Fairen‐Jiménez, D. (2025) · Advanced Materials · doi:10.1002/adma.202412757 · Cited by 52
Xie, W., Yu, X., Yang, Q., Ke, N., Wang, P., Kong, H., Wu, X., Ma, P., Chen, L., Yang, J., et al. (2025) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-1712 · Cited by 49
Guo, J., Wang, S., & Gao, Q. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1258538 · Cited by 47
A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists
Garajová, I., Peroni, M., Gelsomino, F., & Leonardi, F. (2023) · Current Oncology · doi:10.3390/curroncol30110694 · Cited by 48
Ge, W., Wang, Y., Quan, M., Mao, T., Bischof, E. Y., Xu, H., Zhang, X., Li, S., Yue, M., Ma, J., et al. (2024) · Molecular Cancer · doi:10.1186/s12943-024-01965-5 · Cited by 45
Murthy, D., Attri, K. S., Suresh, V., Rajacharya, G. H., Valenzuela, C. A., Thakur, R. K., Zhao, J., Shukla, S. K., Chaika, N. V., LaBreck, D. A., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2315509121 · Cited by 45
Zheng, H., Yang, X., Huang, N., Yuan, S., Li, J., Liu, X., Jiang, Q., Wu, S., Ju, Y., Kleeff, J. H., et al. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02184-8 · Cited by 45
SLC38A5 Modulates Ferroptosis to Overcome Gemcitabine Resistance in Pancreatic Cancer
Kim, M., Kim, H. S., Kang, H. W., Lee, D. E., Hong, W. C., Kim, J.-H., Kim, M., Cheong, J., Kim, H. J., & Park, J. S. (2023) · Cells · doi:10.3390/cells12202509 · Cited by 45
Cai, Z., Yao, H., Chen, J., Ahmed, A. A., Li, C., Hu, X., Tang, X., & Jiang, C. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216689 · Cited by 44
The Multifaceted Role of miR-21 in Pancreatic Cancers
Chen, C., Demirkhanyan, L. H., & Gondi, C. S. (2024) · Cells · doi:10.3390/cells13110948 · Cited by 49
Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies
Rozengurt, E., & Eibl, G. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02499-y · Cited by 49
Liu, Y., Han, J., Hsu, W., LaBella, K. A., Deng, P., Shang, X., de Lara, P. T., Cai, L., Jiang, S., & DePinho, R. A. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0489 · Cited by 43
Sun, G., Wu, Y., Li, J., Yang, M., Xu, H., Li, Y., Tong, P., Shao, R., Liu, Y., & Kong, X. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113642 · Cited by 44
Bodeker, K. L., Smith, B. J., Berg, D., Chandrasekharan, C., Sharif, S., Fei, N. H., Vollstedt, S., Brown, H., Chandler, M. L., Lorack, A. C., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103375 · Cited by 50
Link, J. M., Eng, J. R., Pelz, C., Hawthorne, K., Worth, P. J., Sivagnanam, S., Keith, D., Owen, S., Langer, E. M., Grossblatt-Wait, A., et al. (2025) · Nature Cancer · doi:10.1038/s43018-024-00881-3 · Cited by 44
Xu, X., Wang, X., Liao, Y., Luo, L., & Nel, A. E. (2025) · ACS Nano · doi:10.1021/acsnano.4c14102 · Cited by 44
Lin, H.-Y., Zhu, S., Chen, Y., Lu, J., Xie, C., Liao, C., Huang, X., Li, G., Wu, Y., Li, Z., et al. (2025) · Drug Resistance Updates · doi:10.1016/j.drup.2025.101240 · Cited by 41
Microbiome and pancreatic cancer: time to think about chemotherapy
de Castilhos, J., Tillmanns, K., Blessing, J., Larano, A., Borisov, V., & Stein‐Thoeringer, C. K. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2374596 · Cited by 41
ST6GAL1 sialyltransferase promotes acinar to ductal metaplasia and pancreatic cancer progression
Bhalerao, N., Chakraborty, A., Marciel, M. P., Hwang, J., Britain, C. M., Silva, A. D., Eltoum, I., Jones, R. B., Alexander, K. L., Smythies, L. E., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.161563 · Cited by 39
Ding, L., Lyu, Z., Perles‐Barbacaru, T., Huang, A. Y., Lian, B., Jiang, Y., Roussel, T., Galanakou, C., Giorgio, S., Kao, C., et al. (2023) · Advanced Materials · doi:10.1002/adma.202308262 · Cited by 40
HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells
Luo, Z., Zheng, Q., Ye, S., Li, Y., Chen, J., Fan, C., Chen, J., Lei, Y., Liao, Q., & Yang, X. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06592-y · Cited by 41
Zhang, H., Li, T., Yu, X., Liu, C., Wu, W., Ye, L., & Jin, K. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06589-7 · Cited by 37
Peripheral, central, and chemotherapy-induced neuropathic changes in pancreatic cancer
Jiang, L., Cai, S., Weng, Z., Zhang, S., & Jiang, S. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2024.11.008 · Cited by 37
Tabe, S., Takeuchi, K., Aoshima, K., Okumura, A., Yamamoto, Y., Yanagisawa, K., Eto, R., Matsuo, M., Ueno, Y., Konishi, T., et al. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122838 · Cited by 37
Li, L., Zhang, Z., Zhou, L., Ge, H., Zhao, Y., Gong, Y., Mao, G.-J., & Liu, H. (2024) · Analytical Chemistry · doi:10.1021/acs.analchem.4c00922 · Cited by 35
Pietrobono, S., Sabbadini, F., Bertolini, M., Mangiameli, D., Vita, V. D., Fazzini, F., Lunardi, G., Casalino, S., Scarlato, E., Merz, V., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-0104 · Cited by 34
Li, C., Liu, Y., Liu, C., Chen, F., Xie, Y., Zeh, H. J., Yu, C., Liu, J., Tang, D., & Kang, R. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adp4986 · Cited by 36
Zhang, J., Teng, F., Hu, B., Liu, W., Huang, Y., Wu, J., Wang, Y., Su, H., Yang, S., Zhang, L., et al. (2024) · Advanced Materials · doi:10.1002/adma.202311431 · Cited by 32
Cancer‐associated fibroblast‐derived MMP11 promotes tumor progression in pancreatic cancer
Wang, Z., Guo, X., Li, X., Wang, J., Zhang, N., Amin, B., Xu, G., & Zhu, B. (2024) · Cancer Science · doi:10.1111/cas.16418 · Cited by 32
Artificial Intelligence in Pancreatic Image Analysis: A Review
Liu, W., Zhang, B., Liu, T., Jiang, J., & Liu, Y. (2024) · Sensors · doi:10.3390/s24144749 · Cited by 35
Lencioni, G., Gregori, A., Toledo, B., Rebelo, R., Immordino, B., Amrutkar, M., Xavier, C. P. R., Kocijancic, A., Pandey, D. P., Perán, M., et al. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.09.002 · Cited by 32
Dynamic glycolytic reprogramming effects on dendritic cells in pancreatic ductal adenocarcinoma
Zhang, B., Ohuchida, K., Tsutsumi, C., Shimada, Y., Mochida, Y., Oyama, K., Iwamoto, C., Sheng, N., Fei, S., Shindo, K., et al. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03192-8 · Cited by 34
Combined Flt3L and CD40 agonism restores dendritic cell–driven T cell immunity in pancreatic cancer
Hogg, G. D., Weinstein, A. G., Kingston, N. L., Liu, X., Dres, O. M., Kang, L., Lander, V. E., Kao, Y., Ahmad, F. F., Knolhoff, B. L., et al. (2025) · Science Immunology · doi:10.1126/sciimmunol.adp3978 · Cited by 32
Vahabi, M., Dehni, B., Antomás, I., Giovannetti, E., & Peters, G. J. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10127-w · Cited by 30
Meng, Q., Xie, Y., Sun, K., He, L., Wu, H., Zhang, Q., & Liang, T. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01862-2 · Cited by 30
Zhu, H., Gao, F., Li, Y., Jiang, M., Zhang, Y., Chen, K., Han, L., Xue, S., Wang, K., Fan, Q., et al. (2024) · Nano Today · doi:10.1016/j.nantod.2024.102308 · Cited by 30
Multifunctional GQDs for receptor targeting, drug delivery, and bioimaging in pancreatic cancer
Shukla, M. K., Parihar, A., Karthikeyan, C., Kumar, D., & Khan, R. (2023) · Nanoscale · doi:10.1039/d3nr03161f · Cited by 30
Molecular mechanisms of pancreatic cancer liver metastasis: the role of PAK2
Yang, H., Li, Z., Zhu, S., Wang, W., Zhang, J., Zhao, D., Zhang, M., Zhu, W., Xu, W., & Xu, C. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1347683 · Cited by 30
Nedelcu, A., Mocan, T., Sabău, L. I., MATEA, C. T., Tăbăran, F., Pop, T., Delcea, C., Moșteanu, O., & MOCAN, L. C. (2024) · Scientific Reports · doi:10.1038/s41598-024-63142-4 · Cited by 29
Shen, Q., Liu, J., Zeng, L., Ren, Y., Liao, J., Chen, S., Tang, Y., Zhang, Z., Jiang, M., Liao, H., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113588 · Cited by 31
Chen, Y., Ye, Z., Ma, M., Yang, J., Liu, R., Zhang, Y., Ma, P., & Song, D. (2024) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2024.116241 · Cited by 28
Fu, Y., Tao, J., Gu, Y., Liu, Y., Qiu, J., Su, D., Wang, R., Luo, W., Liu, T., Zhang, F., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00586-x · Cited by 29
The global, regional burden of pancreatic cancer and its attributable risk factors from 1990 to 2021
Yu, W., Zhou, D., Meng, F., Wang, J., Wang, B., Qiang, J., Shen, L., Wang, M., & Fang, H. (2025) · BMC Cancer · doi:10.1186/s12885-025-13471-y · Cited by 33
Pedro, B. A., & Wood, L. D. (2025) · Journal of Clinical Investigation · doi:10.1172/jci191937 · Cited by 35
Total Synthesis of Aleutianamine
Yu, H., Sercel, Z. P., Rezgui, S. P., Farhi, J., Virgil, S. C., & Stoltz, B. M. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c10212 · Cited by 28
Huang, A., Li, Q., Shi, X., Gao, J., Ma, Y., Ding, J., Hua, S., & Zhou, W. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101132 · Cited by 28
Extracellular Vesicles for Disease Treatment
Wang, F., Feng, J., Jin, A., Shao, Y., Shen, M., Ma, J., Lei, L., & Liu, L. (2025) · International Journal of Nanomedicine · doi:10.2147/ijn.s506456 · Cited by 26
Protein induced by vitamin K absence or antagonist II: Experience to date and future directions
Dong, L., Qiu, X., Gao, F., Wang, K., & Xu, X. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.189016 · Cited by 26
Zhu, H., Xu, J., Wang, W., Zhang, B., Liu, J., Liang, C., Hua, J., Meng, Q., Yu, X., & Shi, S. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105098 · Cited by 25
Zhang, J., Lv, S., Peng, X., Liu, H., Guo, J., Liu, Z., Chu, T., Liu, H., Duan, K., Lou, F., et al. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02385-9 · Cited by 26
Maddipati, R. (2025) · Journal of Clinical Investigation · doi:10.1172/jci191943 · Cited by 31
Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer
Aznar, M. A., Good, C. R., Barber-Rotenberg, J. S., Agarwal, S., Wilson, W. V., Watts, A., Zhang, Z., Gonzales, D. M., Donahue, G., Hwang, W.-T., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102301 · Cited by 30
Insights into the relevance of targeting fibroblasts to control cancer
Boeker, V., & Kalluri, R. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102395 · Cited by 25
Hallmarks of perineural invasion in pancreatic ductal adenocarcinoma: new biological dimensions
Sun, Y.-Q., Jiang, W., Liao, X., & Wang, D.-Q. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1421067 · Cited by 32
Zhao, H., Zhang, Y., Liu, H., Wang, Y., & Song, Z. (2024) · BMC Cancer · doi:10.1186/s12885-024-12835-0 · Cited by 24
Wang, Y., Zhou, Q., Luo, W., Yang, X., Zhang, J., Lou, Y., Jin, M., Chen, J., Wu, F., Hou, J., et al. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02968-6 · Cited by 30
Liu, X., Yang, J., Huang, S., Hong, Y., Zhu, Y., Wang, J., Wang, Y., Liang, T., & Bai, X. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.01.023 · Cited by 27
Li, P., Huang, M., Li, M., Li, G., Ma, Y., Zhao, Y. X., Wang, X., Zhang, Y., & Shi, C. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03332-8 · Cited by 26
Intratumoral Cell Neighborhoods Coordinate Outcomes in Pancreatic Ductal Adenocarcinoma
Wattenberg, M. M., Colby, S., Garrido‐Laguna, I., Xue, Y., Chang, R. B., Delman, D., Lee, J., Affolter, K. E., Mulvihill, S. J., Beg, M. S., et al. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.01.013 · Cited by 24
Wang, X., Dai, Z., Lin, X., Zou, X., Wang, R., Tasiheng, Y., Yan, Y., Ma, M., Chen, Y., Cheng, H., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216741 · Cited by 24
Debesset, A., Pilon, C., Meunier, S., Bonizec, O., Richer, W., Thiolat, A., Houppe, C., Ponzo, M., Magnan, J., Caron, J., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-008898 · Cited by 24
Jiang, X., Wang, T., Zhao, B. X., Sun, H., Dong, Y., Ma, Y., Li, Z., Wu, Y., Wang, K., Guan, X., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.101966 · Cited by 26
Yin, L., Cao, C., Lin, J., Wang, Z., Peng, Y., Zhang, K., Xu, C., Yang, R., Zhu, D., Wang, F., et al. (2025) · Journal of Clinical Oncology · doi:10.1200/jco.24.00287 · Cited by 23
Wu, H., Zhang, Q., Cao, Z., Cao, H., Wu, M., Fu, M., Huang, T., Han, X., Chang, X., & Liu, Z. (2025) · iScience · doi:10.1016/j.isci.2025.112681 · Cited by 22
Zeng, L., Wu, Z. K., Yang, J., Zhou, Y., & Chen, R. (2023) · BMC Medicine · doi:10.1186/s12916-023-03202-0 · Cited by 25
CSNK2A1 confers gemcitabine resistance to pancreatic ductal adenocarcinoma via inducing autophagy
Liu, Z., Shi, Y.-H., Xu, Q., Zhao, G.-Y., Zhu, Y., Li, F.-X., Ma, M., Ye, J., Huang, X., Wang, X., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216640 · Cited by 23
Precision Targeting Strategies in Pancreatic Cancer: The Role of Tumor Microenvironment
Vitorakis, N., Gargalionis, A. N., Papavassiliou, K. A., Adamopoulos, C., & Papavassiliou, A. G. (2024) · Cancers · doi:10.3390/cancers16162876 · Cited by 25
Potential of gamma/delta T cells for solid tumor immunotherapy
Zhu, D., Ren, X., Xie, W., Chen, J., Liang, S., Jiang, M., Wang, J., & Zheng, Z. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1466266 · Cited by 24
Metadata
- Authors
- Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A.
- Affiliations
- University of California, Irvine (US)
- University of Michigan (US)
- The University of Texas MD Anderson Cancer Center (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2023-04
- Volume
- 186
- Issue
- 8
- Pages
- 1729-1754
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC10182830
- OpenAlex
- W2182290275
- Semantic Scholar
- 496404429708b3fc52539eb23367c22c672de867
- Cited by
- 1,321
- References
- 302
- Citations by year
- 2026: 406 · 2025: 476 · 2024: 358 · 2023: 81
- FWCI
- 43.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- National Institutes of Health (1r01ca264843-01a1)
- National Cancer Institute (R01-CA264843, P50CA221707, R01CA248160, R01CA220236, R01CA244931, R00CA241357, P30CA046592, U54CA274371, P30CA062203, U01CA274154, R01CA271510, R37CA237421, R01CA260752, U24CA274274, U01CA200468)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- pancreatic ductal adenocarcinoma, tumor microenvironment, cancer metabolism, tumor progression, clinical translation, survival
- MeSH terms
- Humans, Pancreatic Neoplasms, Prognosis, Carcinoma, Pancreatic Ductal, Early Diagnosis, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
