Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine
Open accessAbstract
Over the past decade, our understanding of the diversity of colorectal cancer has expanded significantly, raising hopes of tailoring treatments more precisely for individual patients. A key achievement in this direction was the establishment of the consensus molecular classification, particularly identifying the challenging consensus molecular subtype (CMS) CMS4 associated with poor prognosis. Because of its aggressive nature, extensive research is dedicated to the CMS4 subgroup. Recent years have unveiled molecular and microenvironmental features at the tissue level specific to CMS4 colorectal cancer. This has paved the way for mechanistic studies and the development of preclinical models. Simultaneously, efforts have been made to easily identify patients with CMS4 colorectal cancer. Reassessing clinical trial results through the CMS classification lens has improved our understanding of the therapeutic challenges linked to this subtype. Exploration of the biology of CMS4 colorectal cancer is yielding potential biomarkers and novel treatment approaches. This overview aims to provide insights into the clinico-biological characteristics of the CMS4 subgroup, the molecular pathways driving this subtype, and available diagnostic options. We also emphasize the therapeutic challenges associated with this subtype, offering potential explanations. Finally, we summarize the current tailored treatments for CMS4 colorectal cancer emerging from fundamental and preclinical studies.
AI snapshot
Written from the paper’s full text.
TL;DR
CMS4 colorectal cancer is an aggressive, stroma-rich, mesenchymal subtype with poor prognosis and limited benefit from standard chemotherapy. This review summarizes its clinical, histologic, and molecular hallmarks, diagnostic strategies, and emerging targeted or stroma-directed treatment approaches.
Key findings
- CMS4 accounts for about 20%–25% of colorectal cancer cases and is associated with worse overall and relapse-free survival; prevalence increases with stage, from 10% in stage I to 38.5% in stage IV.
- No genomic feature is specific to CMS4; key biological features include TGFβ pathway activation, YAP/TAZ signaling, PrPC/ILK signaling, elevated AKT3 and KIT, reduced mitochondrial complex I activity, and altered splicing.
- Patients with stage II/III CMS4 benefit less from adjuvant chemotherapy, and in the metastatic setting irinotecan-based regimens have superior efficacy compared with oxaliplatin-based regimens; the PanaMa trial showed an OS benefit from adding panitumumab to 5-FU and folinic acid maintenance in CMS4 patients.
- Selected CMS4 clinical signals include imatinib suppressing mesenchymal genes in posttreatment samples (n = 5), napabucasin plus pembrolizumab producing an immune-related objective response rate of 33% (2 of 6 CMS4 patients), nintedanib increasing PFS from 1.3 to 2.2 months (n = 60 nintedanib-treated and n = 59 placebo CMS4 patients), and regorafenib increasing PFS versus placebo (n = 26 CMS4 patients).
Methods
- Narrative overview/review synthesizing published clinical, molecular, and preclinical literature on CMS4 colorectal cancer, with summary tables and proposed pathway figures.
- No new patient cohort, experimental data, or formal systematic review/meta-analysis is reported; cited evidence includes clinical trials, preclinical models, organoids, mouse models, and diagnostic studies.
Limitations
- Stated: data on CMS classes were mostly gained from United States/European populations, and the potential impact of race or ethnicity on CMS distribution remains to be evaluated.
- Stated: the CMS classification was built on full transcriptome profiling, which is not yet compatible with day-to-day patient management; circulating PrPC levels could not be assessed for CMS discrimination because CMS classification was not available for those patients.
- Evident: as a narrative review, there is no systematic search or quantitative synthesis, and several therapeutic signals come from small CMS4 subgroups (e.g., n = 5, n = 6, n = 26) and require validation.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
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Claims the paper makes
0 of 101 cited sources checked · 0 supported · 0 flagged
- Premisecitation
CMS4 tumors have stromal enrichment.
“A second outstanding and undisputed hallmark of CMS4 tumors is their stromal enrichment, which emerged both from transcriptomic signature (2) and histologic analyses (29).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [2] Becht, 2016, Immune and stromal classification of colorectal cancer is associated with molecular subtypes and relevant for precision immunotherapy, Clin Cancer Res source
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- cites [29] Sirinukunwattana, 2021, Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning, Gut source
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- Premisecitation
Genetic alterations in SMAD4 and TGFBR2 are not overrepresented in the CMS4 subgroup.
“such genetic alterations are not overrepresented in the CMS4 subgroup (1)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Guinney, 2015, The consensus molecular subtypes of colorectal cancer, Nat Med source
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- Premisecitation
The consensus molecular subtype CMS4 of colorectal cancer is associated with poor prognosis, including worse overall survival and relapse-free survival.
“the challenging consensus molecular subtype (CMS) CMS4 associated with poor prognosis”
- Also stated in: § Introduction · plain
“The so-called “mesenchymal” CMS4 subgroup (23% of patients) is that of worse overall survival (OS) and relapse-free survival (1)”
- Also stated in: § Clinical hallmarks · plain
“CMS4 colon cancers stand out from other subtypes by their aggressiveness and poor prognosis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Guinney, 2015, The consensus molecular subtypes of colorectal cancer, Nat Med source
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- Also stated in: § Introduction · plain
- Premisecitation
CMS4 tumors exhibit a mesenchymal morphology.
“CMS4 tumors exhibit a mesenchymal morphology”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Guinney, 2015, The consensus molecular subtypes of colorectal cancer, Nat Med source
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- Premisecitation
TGFβ fosters the emergence of an immunosuppressive contexture.
“and that it fosters the emergence of an immunosuppressive contexture”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] Tauriello, 2018, TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis, Nature source
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- Premisecitation
The CMS4 subtype is enriched at the invasive margin as compared with the tumor core.
“multisampling analyses have revealed an enrichment in the CMS4 subtype at the invasive margin as compared with the tumor core (11).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Dunne, 2017, Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification, Nat Commun source
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- Premisecitation
The enrichment of CMS4 tumors in CAFs is a shared outstanding characteristic.
“Whatever their intrinsic subtype correspondence, the enrichment of CMS4 tumors in CAFs is a shared outstanding characteristic.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
CMS4-like colon cancer cells themselves respond to TGFβ and control the expression of a number of CMS4-specific genes through this pathway.
“we reported that CMS4-like colon cancer cells themselves respond to TGFβ, and notably control the expression of a number of CMS4-specific genes through this pathway (35).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] Le Corre, 2019, The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer, EBioMedicine source
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- Premisecitation
CMS4 is present in the vast majority of peritoneal metastases.
“was shown to be present in the vast majority of peritoneal metastases (24).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] Lenos, 2022, Molecular characterization of colorectal cancer related peritoneal metastatic disease, Nat Commun source
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- Premisecitation
The induction of some TGFβ target genes does not require SMAD4.
“it is now apparent that the induction of some TGFβ target genes does not require SMAD4 (37).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] Massagué, 2023, TGF-β signaling in health and disease, Cell source
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- Premisecitation
No genomic feature is specific to CMS4 tumors.
“no genomic feature is specific to CMS4 tumors (1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Guinney, 2015, The consensus molecular subtypes of colorectal cancer, Nat Med source
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- Premisecitation
CMS4 tumors are characterized by an abundant expression of the master EMT transcription factor ZEB1 easily detectable by IHC.
“are characterized by an abundant expression of the master EMT transcription factor ZEB1 easily detectable by IHC (28).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] Trinh, 2016, Practical and robust identification of molecular subtypes in colorectal cancer by immunohistochemistry, Clin Cancer Res source
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- Premisecitation
ZEB2 activation is a key downstream event in the reprogramming of CMS2 cancer cells into a CMS4 subtype in response to visceral adipose-derived factors, through a STAT3-miR200 axis.
“ZEB2 activation was also depicted as a key downstream event in the reprogramming of CMS2 cancer cells into a CMS4 subtype in response to visceral adipose-derived factors, through a STAT3-miR200 axis (21).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Di Franco, 2021, Adipose stem cell niche reprograms the colorectal cancer stem cell metastatic machinery, Nat Commun source
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- Premisecitation
CMS4 colorectal cancer may alternatively originate from CMS3 tubular adenomas.
“CMS4 colorectal cancer may alternatively originate from CMS3 tubular adenomas (TA; Fig. 1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] van de Weerd, 2023, Consensus molecular subtype transition during progression of colorectal cancer, J Pathol source
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- Interpretationreasoning
TGFβ is central in the tumor-intrinsic and -extrinsic traits of CMS4 colorectal cancer.
“On this basis, it can be surmised that TGFβ is central in the tumor-intrinsic and -extrinsic traits of CMS4 colorectal cancer.”
Quote in the paperSubstantial claim - Premisecitation
YAP and TAZ expression is significantly increased in CMS4 tumors.
“YAP and TAZ, the main effectors of the Hippo pathway, whose expression was shown to be significantly increased in CMS4 tumors in reverse phase protein arrays (1).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Guinney, 2015, The consensus molecular subtypes of colorectal cancer, Nat Med source
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- Premisecitation
CMS4 colorectal cancer is consistently associated with a dismal outcome, including at early stage.
“CMS4 colorectal cancer is consistently associated with a dismal outcome (1, 26), including at early stage (27).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [1] Guinney, 2015, The consensus molecular subtypes of colorectal cancer, Nat Med source
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- cites [26] Ten Hoorn, 2022, Clinical value of consensus molecular subtypes in colorectal cancer: a systematic review and meta-analysis, J Natl Cancer Inst source
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- cites [27] Haasnoot, 2020, Associations of non-pedunculated T1 colorectal adenocarcinoma outcome with consensus molecular subtypes, immunoscore, and microsatellite status: a multicenter case-cohort study, Mod Pathol source
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- Premisecitation
PrPC controls the expression of many CMS4-specific genes in colon cancer cells through diverse signaling intermediates.
“we introduced PrPC, a plasma membrane-tethered protein endowed with the capacity to participate in signal transduction events (38), as a key protagonist of CMS4 colon cancer, controlling the expression of many CMS4-specific genes in colon cancer cells through diverse signaling intermediates (35, 39).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [35] Le Corre, 2019, The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer, EBioMedicine source
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- cites [39] Ghazi, 2021, Prognostic value of the PrPC-ILK-IDO1 axis in the mesenchymal colorectal cancer subtype, Oncoimmunology source
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- Premisecitation
The concentration of soluble TGFβ in the supernatant of colon cancer cells is partly controlled by the cellular prion protein PrPC.
“we recently brought some insight into this issue by showing that the concentration of soluble TGFβ in the supernatant of colon cancer cells is partly controlled by the cellular prion protein PrPC (35).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] Le Corre, 2019, The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer, EBioMedicine source
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- Premisecitation
The CMS4 subtype is associated with tumor budding.
“several studies have documented an association between the CMS4 subtype and tumor budding, defined as a single tumor cell or tumor cluster of up to four cells at the invasive margin (29–31)”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [29] Sirinukunwattana, 2021, Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning, Gut source
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- cites [30] De Smedt, 2017, Expression profiling of budding cells in colorectal cancer reveals an EMT-like phenotype and molecular subtype switching, Br J Cancer source
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- cites [31] Trinh, 2018, Tumour budding is associated with the mesenchymal colon cancer subtype and RAS/RAF mutations: a study of 1320 colorectal cancers with Consensus Molecular Subgroup (CMS) data, Br J Cancer source
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- Premisecitation
Tumor budding is associated with poor prognosis.
“a trait that is associated with poor prognosis (32).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] Basile, 2022, Tumor budding is an independent prognostic factor in stage III colon cancer patients: a post-hoc analysis of the IDEA-France phase III trial (PRODIGE-GERCOR), Ann Oncol source
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- Premisecitation
TGFβ can direct human organoid cultures to a CMS4 profile.
“Follow-up studies have documented that TGFβ can direct human organoid cultures to a CMS4 profile (20)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Fessler, 2016, TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype, EMBO Mol Med source
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- Premisecitation
The TGFβ pathway is enriched in CMS4 colorectal cancer.
“One of the most scrutinized pathways originally found to be enriched in CMS4 colorectal cancer is the TGFβ pathway (1).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Guinney, 2015, The consensus molecular subtypes of colorectal cancer, Nat Med source
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- Interpretationcitation
The CMS4 tumor state arises from the progression of a less aggressive state, rather than originating from a distinct carcinogenesis pathway, perhaps with the exception of inflammation-induced colorectal cancer.
“Altogether, several works based on paired tumor regions (11, 19, 30) support the notion that the CMS4 tumor state arises from the progression of a less aggressive state, rather than originating from a distinct carcinogenesis pathway, perhaps with the exception of inflammation-induced colorectal cancer (25).”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [11] Dunne, 2017, Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification, Nat Commun source
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- cites [19] van de Weerd, 2023, Consensus molecular subtype transition during progression of colorectal cancer, J Pathol source
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- cites [30] De Smedt, 2017, Expression profiling of budding cells in colorectal cancer reveals an EMT-like phenotype and molecular subtype switching, Br J Cancer source
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- cites [25] Rajamäki, 2021, Genetic and epigenetic characteristics of inflammatory bowel disease-associated colorectal cancer, Gastroenterology source
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- Premisecitation
The proportion of CMS4 cases increases with disease stage, ranging from 10% in stage 1 to 38.5% in stage 4 patients.
“the proportion of CMS4 cases was shown to gradually increase with stage, ranging from 10% in stage 1 to 38.5% in stage 4 patients (16).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Coebergh van den Braak, 2020, Interconnectivity between molecular subtypes and tumor stage in colorectal cancer, BMC Cancer source
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- Premisecitation
Mixed CMS tumors with a CMS4 component also have a poor outcome.
“This also holds for mixed CMS tumors with a CMS4 component (13).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Marisa, 2021, Intratumor CMS heterogeneity impacts patient prognosis in localized colon cancer, Clin Cancer Res source
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- Premisecitation
The profile of inflammatory bowel disease-related colorectal cancer mainly falls in the CMS4 group.
“the profile of inflammatory bowel disease–related colorectal cancer mainly falls in the CMS4 group (25).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [25] Rajamäki, 2021, Genetic and epigenetic characteristics of inflammatory bowel disease-associated colorectal cancer, Gastroenterology source
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- Premisecitation
The CMS4 profile may come up upon metastasis in various tissues.
“The CMS4 profile may also come up upon metastasis in various tissues (10, 22, 23)”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [10] Eide, 2021, Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer, NPJ Genomic Med source
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- cites [22] Piskol, 2019, A clinically applicable gene-expression classifier reveals intrinsic and extrinsic contributions to consensus molecular subtypes in primary and metastatic colon cancer, Clin Cancer Res source
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- cites [23] Trumpi, 2017, Neoadjuvant chemotherapy affects molecular classification of colorectal tumors, Oncogenesis source
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- Premisecitation
Imatinib suppresses mesenchymal genes in posttreatment samples from 5 patients with primary CMS4 colorectal cancer who consented to treatment prior to surgery.
“| PDGF pathway | Imatinib | Suppression of mesenchymal genes in posttreatment samples (n = 5 patients with primary CMS4 colorectal cancer who consented to treatment prior to surgery) | (63) |”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [63] Peters, 2022, Consensus molecular subtype 4 (CMS4)-targeted therapy in primary colon cancer: a proof-of-concept study, Front Oncol source
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- Premisecitation
Coculture with CAFs promotes increased resistance to SN-38 and gefitinib in CMS4 compared with CMS2 patient-derived tumor organoids.
“A very recent study reported that coculture with CAFs promotes an increased resistance to SN-38 (irinotecan active metabolite) and gefitinib of CMS4 compared with CMS2 patient-derived tumor organoids (53).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [53] Farin, 2023, Colorectal cancer organoid-stroma biobank allows subtype-specific assessment of individualized therapy responses, Cancer Discov source
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- Interpretationcitation
The stroma-rich hallmark of CMS4 colorectal cancer may represent a promising therapeutic vulnerability.
“Thus, the stroma-rich hallmark of CMS4 colorectal cancer may represent a promising therapeutic vulnerability, as suggested by Dunne and colleagues (73).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [73] Corry, 2022, Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer, Gut source
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- Interpretationcitation
The immunosuppressive trait of CMS4 is reinforced by CAFs.
“it is likely that the immunosuppressive trait of CMS4 is reinforced by CAFs (55).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [55] Chen, 2021, Clinical and therapeutic relevance of cancer-associated fibroblasts, Nat Rev Clin Oncol source
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- Premisecitation
Stromal contribution to resistance in CMS4 colorectal cancer occurs through ECM deposition and cancer cell insulation.
“through ECM deposition and cancer cells insulation (54)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [54] Biffi, 2021, Diversity and biology of cancer-associated fibroblasts, Physiol Rev source
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- Interpretationcitation
Cancer cells and CAF-derived factors, including TGFβ and PDGF, promote endothelial cell infiltration and angiogenesis, which are hallmarks of CMS4.
“both cancer cells and CAF-derived factors, including TGFβ and PDGF, are expected to promote endothelial cell infiltration and angiogenesis, again hallmarks of CMS4 (2).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] Becht, 2016, Immune and stromal classification of colorectal cancer is associated with molecular subtypes and relevant for precision immunotherapy, Clin Cancer Res source
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- Premisecitation
In the metastatic setting, irinotecan-based regimens have superior efficacy compared with those with an oxaliplatin backbone.
“in the metastatic setting, irinotecan-based regimens have superior efficacy compared with those with an oxaliplatin backbone (26).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Ten Hoorn, 2022, Clinical value of consensus molecular subtypes in colorectal cancer: a systematic review and meta-analysis, J Natl Cancer Inst source
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- Premisecitation
The PanaMa trial showed an OS benefit from the addition of panitunimab to 5-FU and FA maintenance in CMS4 patients.
“Recently, results from the PanaMa trial showed an OS benefit from the addition of panitunimab to 5-FU and FA maintenance in CMS4 patients (61).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [61] Stahler, 2023, Consensus molecular subtypes as biomarkers of fluorouracil and folinic acid maintenance therapy with or without panitumumab in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212), J Clin Oncol source
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- Premisecitation
Positive responses have been reported for CMS4 patients treated with the triple tyrosine kinase inhibitor nintedanib.
“(iii) the triple tyrosine kinase inhibitor nintedanib (LUME-Colon1 trial; ref. 65)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [65] Lenz, 2021, Association of consensus molecular subtypes and molecular markers with clinical outcomes in patients with metastatic colorectal cancer: biomarker analyses from LUME-Colon 1, Clin Colorectal Cancer
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- Interpretationcitation
PrPC neutralization could have the combined advantage of reducing both TGFβ and PDGF signaling.
“or PrPC, whose neutralization could have the combined advantage of reducing both TGFβ and PDGF signaling (68).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [68] Mouillet-Richard, 2022, A proof of concept for targeting the PrPC - Amyloid β peptide interaction in basal prostate cancer and mesenchymal colon cancer, Oncogene source
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- Interpretationcitation
HSP90, PAK2, and AKT3 have emerged as candidate targets from preclinical studies of CMS4 colorectal cancer.
“Other candidate targets have emerged from preclinical studies, including HSP90, combined with 5-FU (7), PAK2 (67) or AKT3 (42)”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [7] Sveen, 2018, Colorectal cancer consensus molecular subtypes translated to preclinical models uncover potentially targetable cancer cell dependencies, Clin Cancer Res source
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- cites [67] Buikhuisen, 2023, Subtype-specific kinase dependency regulates growth and metastasis of poor-prognosis mesenchymal colorectal cancer, J Exp Clin Cancer Res CR
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- cites [42] Buikhuisen, 2021, AKT3 expression in mesenchymal colorectal cancer cells drives growth and is associated with epithelial-mesenchymal transition, Cancers source
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- Premisecitation
PAK2 shRNA reduced intraperitoneal metastases in preclinical models of CMS4 colorectal cancer.
“| PAK2 | PAK2 shRNA | Reduced intraperitoneal metastases | (67) |”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [67] Buikhuisen, 2023, Subtype-specific kinase dependency regulates growth and metastasis of poor-prognosis mesenchymal colorectal cancer, J Exp Clin Cancer Res CR
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- Premisecitation
Patients with stage II and III CMS4 colorectal cancer benefit less from adjuvant chemotherapy than other subtypes.
“It is now quite well established that patients with stage II and III CMS4 colorectal cancer benefit less from adjuvant chemotherapy than other subtypes”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Ten Hoorn, 2022, Clinical value of consensus molecular subtypes in colorectal cancer: a systematic review and meta-analysis, J Natl Cancer Inst source
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- Premisecitation
Stromal contribution to resistance in CMS4 colorectal cancer occurs through co-migration with cancer cells to metastatic sites.
“co-migration with cancer cells to metastatic sites (70)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [70] Gonzalez-Zubeldia, 2015, Co-migration of colon cancer cells and CAFs induced by TGFβ₁ enhances liver metastasis, Cell Tissue Res source
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- Premisecitation
PrPC is increased in CMS4 tumors.
“One candidate circulating biomarker is PrPC, which we found to be increased in CMS4 tumors”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [35] Le Corre, 2019, The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer, EBioMedicine source
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- Premisecitation
Luminespib combined with 5-FU reduced tumor growth in preclinical models of CMS4 colorectal cancer.
“| HSP90 | Luminespib + 5-FU | Reduced tumor growth | (7) |”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7] Sveen, 2018, Colorectal cancer consensus molecular subtypes translated to preclinical models uncover potentially targetable cancer cell dependencies, Clin Cancer Res source
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- Premisecitation
Neutralizing antibodies against PrPC reduced expression of CMS4 genes and soluble TGFβ levels in preclinical models.
“| PrPC | Neutralizing antibodies | Reduced expression of CMS4 genes and soluble TGFβ levels | (68) |”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [68] Mouillet-Richard, 2022, A proof of concept for targeting the PrPC - Amyloid β peptide interaction in basal prostate cancer and mesenchymal colon cancer, Oncogene source
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- Premisecitation
Nintedanib increased progression-free survival from 1.3 to 2.2 months in CMS4 patients with metastatic colorectal cancer (n = 60 nintedanib-treated and n = 59 placebo).
“| Receptor tyrosine kinases | Nintedanib | Increased progression-free survival (PFS) from 1.3 to 2.2 months (n = 60 nintedanib-treated and n = 59 placebo CMS4 patients with metastatic colorectal cancer) | (65) |”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [65] Lenz, 2021, Association of consensus molecular subtypes and molecular markers with clinical outcomes in patients with metastatic colorectal cancer: biomarker analyses from LUME-Colon 1, Clin Colorectal Cancer
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- Premisecitation
The detection of FAP through PET imaging as a surrogate of CMS4 colorectal cancer appears extremely promising.
“the detection of FAP (fibroblast activated protein) through PET imaging as a surrogate of CMS4 colorectal cancer appears extremely promising (60).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [60] Strating, 2022, Fibroblast activation protein identifies consensus molecular subtype 4 in colorectal cancer and allows its detection by 68Ga-FAPI-PET imaging, Br J Cancer source
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- Premisecitation
Napabucasin plus pembrolizumab produced an immune-related objective response rate of 33% (2 of 6) in CMS4 patients with metastatic colorectal cancer.
“| Combined STAT3 and PD-1 | Napabucasin + pembrolizumab | Immune-related objective response rate in 33% of patients (2 of 6 CMS4 patients with metastatic colorectal cancer) | (64) |”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [64] Kawazoe, 2020, Multicenter phase I/II trial of napabucasin and pembrolizumab in patients with metastatic colorectal cancer (EPOC1503/SCOOP trial), Clin Cancer Res source
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- Premisecitation
Dual TGFβ and PD-L1 inhibition with bintrafust alfa was not effective in patients with liver metastasis.
“dual TGFβ and PD-L1 inhibition with bintrafust alfa was not effective in patients with liver metastasis (62).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [62] Morris, 2022, Bintrafusp alfa, an anti-PD-L1:TGF-β trap fusion protein, in patients with ctDNA-positive, liver-limited metastatic colorectal cancer, Cancer Res Commun source
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- Premisecitation
CAFs reinforce the CMS4 traits of cancer cells.
“studies based on coculture experiments have unambiguously demonstrated that CAFs reinforce the CMS4 traits of cancer cells (53).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [53] Farin, 2023, Colorectal cancer organoid-stroma biobank allows subtype-specific assessment of individualized therapy responses, Cancer Discov source
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- Premisecitation
Positive responses have been reported for CMS4 patients treated with the multikinase inhibitor regorafenib.
“(iv) the multikinase inhibitor regorafenib (CORRECT trial; ref. 66; Table 2).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [66] Teufel, 2015, Molecular subtypes and outcomes in regorafenib-treated patients with metastatic colorectal cancer (mCRC) enrolled in the CORRECT trial, J Clin Oncol source
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- Premisecitation
Intratumor heterogeneity is associated with the notable dismal prognosis of CMS4-associated combinations.
“Finally, one challenging issue arising from intratumor heterogeneity pertains to the notable dismal prognosis of CMS4-associated combinations (13).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Marisa, 2021, Intratumor CMS heterogeneity impacts patient prognosis in localized colon cancer, Clin Cancer Res source
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- Premisecitation
Positive responses have been reported for CMS4 patients treated with a combination of napabucasin and pembrolizumab.
“(ii) a combination of napabucasin (a STAT3 inhibitor) and pembrolizumab (EPOC1503/SCOOP trial; ref. 64)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [64] Kawazoe, 2020, Multicenter phase I/II trial of napabucasin and pembrolizumab in patients with metastatic colorectal cancer (EPOC1503/SCOOP trial), Clin Cancer Res source
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- Premisecitation
Positive responses have been reported for CMS4 patients treated with imatinib before surgery, in a very limited number of patients.
“positive responses have been reported for CMS4 patients treated with (i) imatinib—targeting the PDGF pathway—before surgery (ImPACCT trial), however in a very limited number of patients (63)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [63] Peters, 2022, Consensus molecular subtype 4 (CMS4)-targeted therapy in primary colon cancer: a proof-of-concept study, Front Oncol source
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- Premisecitation
A qRT-PCR-based test based on the expression of several effectors of the PDGF pathway and the KIT receptor has a high degree of robustness.
“the group of O. Kranenburg proposed a qRT-PCR–based test based on the expression of several effectors of the PDGF pathway as well as the KIT receptor, with a high degree of robustness (58).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [58] Ubink, 2017, A novel diagnostic tool for selecting patients with mesenchymal-type colon cancer reveals intratumor subtype heterogeneity, J Natl Cancer Inst source
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- Rests on an assumption: The CMS classification is not yet compatible with the day-to-day management of patients with colorectal cancer.
- Premisecitation
NanoString-based classifiers have been developed for CMS4 colorectal cancer.
“A number of teams, including ours, have further developed NanoString-based classifiers (13, 22, 59).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [13] Marisa, 2021, Intratumor CMS heterogeneity impacts patient prognosis in localized colon cancer, Clin Cancer Res source
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- cites [22] Piskol, 2019, A clinically applicable gene-expression classifier reveals intrinsic and extrinsic contributions to consensus molecular subtypes in primary and metastatic colon cancer, Clin Cancer Res source
Not checked in the free run.
- cites [59] Morris, 2021, Development and validation of a gene signature classifier for consensus molecular subtyping of colorectal carcinoma in a CLIA-certified setting, Clin Cancer Res source
Not checked in the free run.
- Premisecitation
Combining TGFβ targeting with immune checkpoint blockade has demonstrated efficacy in in vivo CMS4 colorectal cancer models.
“combining TGFβ targeting with immune checkpoint blockade has demonstrated efficacy in in vivo CMS4 colorectal cancer models (34).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] Tauriello, 2018, TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis, Nature source
Not checked in the free run.
- Premisecitation
Combined MEK and SRC inhibition has a gene expression signature of sensitivity in CMS4 colorectal cancer.
“| Combined MEK and SRC | | Gene expression signature of sensitivity | (69) |”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [69] Yang, 2022, An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy, BMC Cancer source
Not checked in the free run.
- Premisecitation
The FOLFIRI + cetuximab combination (for RAS wild-type patients) is superior to the FOLFIRI + bevacizumab combination.
“the FOLFIRI + cetuximab combination (for RAS wild-type patients) is superior to the FOLFIRI + bevacizumab combination (26).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] Ten Hoorn, 2022, Clinical value of consensus molecular subtypes in colorectal cancer: a systematic review and meta-analysis, J Natl Cancer Inst source
Not checked in the free run.
- Premisecitation
Regorafenib increased progression-free survival versus placebo in CMS4 patients with metastatic colorectal cancer (n = 26).
“| Kinases | Regorafenib | Increased PFS with regorafenib vs. placebo (n = 26 CMS4 patients with metastatic colorectal cancer) | (66) |”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [66] Teufel, 2015, Molecular subtypes and outcomes in regorafenib-treated patients with metastatic colorectal cancer (mCRC) enrolled in the CORRECT trial, J Clin Oncol source
Not checked in the free run.
- Premisecitation
KRAS-mutated CMS4 colorectal cancer was predicted to respond to combined MEK and SRC inhibition.
“From gene expression signatures studies, KRAS-mutated CMS4 colorectal cancer was further predicted to respond to combined MEK and SRC inhibition (69).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [69] Yang, 2022, An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy, BMC Cancer source
Not checked in the free run.
- Premisecitation
MK2206 reduced cell growth in preclinical models of CMS4 colorectal cancer (AKT3 target).
“| AKT3 | MK2206 | Reduced cell growth | (42) |”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [42] Buikhuisen, 2021, AKT3 expression in mesenchymal colorectal cancer cells drives growth and is associated with epithelial-mesenchymal transition, Cancers source
Not checked in the free run.
- Interpretationcitation
The strong TGFβ impregnation of CMS4 colorectal cancer is likely to build an immunotolerant environment.
“the strong TGFβ impregnation of CMS4 colorectal cancer is likely to build an immunotolerant environment, as reviewed recently (56).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [56] Tauriello, 2022, Overcoming TGFβ-mediated immune evasion in cancer, Nat Rev Cancer source
Not checked in the free run.
- Rests on an assumption: The molecular mechanisms behind the resistance of CMS4 colorectal cancer to 5-FU and oxaliplatin-based regimens are not fully understood.
- Interpretationcitation
The prevalent stromal contingent in CMS4 colorectal cancer is likely to contribute to resistance mechanisms.
“In terms of TME contexture, the prevalent stromal contingent is likely to contribute to resistance mechanisms, for instance through ECM deposition and cancer cells insulation (54), co-migration with cancer cells to metastatic sites (70), chemotherapy-induced secretome fostering metastasis, angiogenesis, immune evasion and/or drug resistance (71), or even drug retention, as demonstrated in the case”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [54] Biffi, 2021, Diversity and biology of cancer-associated fibroblasts, Physiol Rev source
Not checked in the free run.
- cites [70] Gonzalez-Zubeldia, 2015, Co-migration of colon cancer cells and CAFs induced by TGFβ₁ enhances liver metastasis, Cell Tissue Res source
Not checked in the free run.
- cites [71] Linares, 2020, Determinants and functions of CAFs secretome during cancer progression and therapy, Front Cell Dev Biol source
Not checked in the free run.
- Premisecitation
PrPC is elevated in plasma derived from patients with metastatic colorectal cancer.
“and elevated in plasma derived from patients with metastatic colorectal cancer (35).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] Le Corre, 2019, The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer, EBioMedicine source
Not checked in the free run.
- Premisecitation
Stromal contribution to resistance in CMS4 colorectal cancer occurs through chemotherapy-induced secretome fostering metastasis, angiogenesis, immune evasion and/or drug resistance.
“chemotherapy-induced secretome fostering metastasis, angiogenesis, immune evasion and/or drug resistance (71)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [71] Linares, 2020, Determinants and functions of CAFs secretome during cancer progression and therapy, Front Cell Dev Biol source
Not checked in the free run.
- Premisecitation
Stromal contribution to resistance in CMS4 colorectal cancer occurs through drug retention, as demonstrated for oxaliplatin.
“or even drug retention, as demonstrated in the case of oxaliplatin (72)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [72] Linares, 2023, Long-term platinum-based drug accumulation in cancer-associated fibroblasts promotes colorectal cancer progression and resistance to therapy, Nat Commun source
Not checked in the free run.
- Classified as probably not a substantial claim. 4
- May combine two claims. 6
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCombined TGFβ targeting and immune checkpoint blockade may represent an attractive therapeutic strategy for CMS4 colorectal cancer.
“leading to the proposition that combined TGFβ targeting and immune checkpoint blockade may represent an attractive therapeutic strategy for CMS4 colorectal cancer (34).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] Tauriello, 2018, TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis, Nature source
Not checked in the free run.
May combine two claims.
PremisecitationThe CMS4 subtype is barely if not detected in adenomas and arises at the carcinoma stage, notably after transition from an indolent CMS3 subtype.
“A consensus that emerged from several studies is that the CMS4 subtype is barely if not detected in adenomas and arises at the carcinoma stage (17, 18), notably after transition from an indolent CMS3 subtype.”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationCancer cells from CMS4 colorectal cancer reside in either a fibrotic intrinsic CMS2 (iCMS2) or iCMS3 state according to the type of lesion: TA-type CMS4 correspond to the iCMS2-F class, while SSL-type CMS4 correspond to the iCMS3-F class.
“According to the single-cell study by Joanito and colleagues (14), cancer cells from CMS4 colorectal cancer reside in either a fibrotic intrinsic CMS2 (iCMS2) or iCMS3 state according to the type of lesion: TA-type CMS4 correspond to the iCMS2-F class (F standing for fibrotic), while SSL-type CMS4 correspond to the iCMS3-F class.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] Joanito, 2022, Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer, Nat Genet source
Not checked in the free run.
May combine two claims.
PremisecitationActivation of YAP and/or TAZ is a cardinal trait of CMS4 colorectal cancer, similar to that of TGFβ.
“Activation of YAP and/or TAZ appears to represent a cardinal trait of CMS4 colorectal cancer, similar to that of TGFβ (40).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [40] Mouillet-Richard, 2020, YAP/TAZ signalling in colorectal cancer: lessons from consensus molecular subtypes, Cancers source
Not checked in the free run.
May combine two claims.
PremisecitationElevated AKT3 and KIT, reduced mitochondrial respiratory complex I activity, and modified alternative splicing landscape are biological hallmarks of CMS4.
“Among other biological hallmarks of this subtype shown to contribute to CMS4 traits feature elevated AKT3 (42) and KIT (43), reduced mitochondrial respiratory complex I activity (44)—possibly resulting from KIT overexpression (43)—or modified alternative splicing landscape (45).”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [42] Buikhuisen, 2021, AKT3 expression in mesenchymal colorectal cancer cells drives growth and is associated with epithelial-mesenchymal transition, Cancers source
Not checked in the free run.
- cites [43] Küçükköse, 2022, KIT promotes tumor stroma formation and counteracts tumor-suppressive TGFβ signaling in colorectal cancer, Cell Death Dis source
Not checked in the free run.
- cites [44] Bastin, 2023, Downregulation of mitochondrial complex I induces ROS production in colorectal cancer subtypes that differently controls migration, J Transl Med source
Not checked in the free run.
- cites [45] Xu, 2022, Alternative splicing downstream of EMT enhances phenotypic plasticity and malignant behavior in colon cancer, Elife source
Not checked in the free run.
May combine two claims.
PremisecitationILK is overexpressed in CMS4 colon cancer and acts as a relay downstream from PrPC to activate YAP/TAZ signaling.
“Another effector is the integrin linked kinase (ILK), which we found to be overexpressed in CMS4 colon cancer and to act as a relay downstream from PrPC to activate YAP/TAZ signaling (39).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [39] Ghazi, 2021, Prognostic value of the PrPC-ILK-IDO1 axis in the mesenchymal colorectal cancer subtype, Oncoimmunology source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCMS4 accounts for 20%-25% of colorectal cancer cases.
“While the CMS4 group globally accounts for 20%–25% of colorectal cancer cases (1)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Guinney, 2015, The consensus molecular subtypes of colorectal cancer, Nat Med source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationArtificial intelligence opens new avenues for colorectal cancer classification with a high degree of robustness.
“artificial intelligence is now opening up new avenues for colorectal cancer classification, with a high degree of robustness (29).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Sirinukunwattana, 2021, Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning, Gut source
Not checked in the free run.
May combine two claims.
InterpretationcitationTGFβ and Kynurenine are involved in the immunotolerant CMS4 tumor microenvironment.
“Regarding the immunotolerant CMS4 TME, we posit an involvement of TGFβ (56) and Kynurenine (57), both produced by cancer cells under the control of PrPC (35, 39)”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [56] Tauriello, 2022, Overcoming TGFβ-mediated immune evasion in cancer, Nat Rev Cancer source
Not checked in the free run.
- cites [57] Platten, 2019, Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond, Nat Rev Drug Discov source
Not checked in the free run.
- cites [35] Le Corre, 2019, The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer, EBioMedicine source
Not checked in the free run.
- cites [39] Ghazi, 2021, Prognostic value of the PrPC-ILK-IDO1 axis in the mesenchymal colorectal cancer subtype, Oncoimmunology source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIHC defines CMS4 as pMMR, CDX2-negative and FRMD6, HTR2B and ZEB1-positive tumors.
“IHC, CMS4 being defined as pMMR, CDX2-negative and FRMD6, HTR2B and ZEB1-positive tumors (28).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] Trinh, 2016, Practical and robust identification of molecular subtypes in colorectal cancer by immunohistochemistry, Clin Cancer Res source
Not checked in the free run.
The paper relies on this without support.
The CMS classification is not yet compatible with the day-to-day management of patients with colorectal cancer.
“The CMS classification was built on full transcriptome profiling, which is not yet compatible with the day-to-day management of patients with colorectal cancer in the clinics.”
The paper relies on this without support.
The molecular mechanisms behind the resistance of CMS4 colorectal cancer to 5-FU and oxaliplatin-based regimens are not fully understood.
“The molecular mechanisms behind the resistance of CMS4 colorectal cancer to 5-FU and oxaliplatin-based regimens are not fully understood.”
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?
CMS4 tumours are marked by stromal signatures including cancer-associated fibroblasts and endothelial cells.
“CMS1 tumours show a strong association with dMMR/MSI-H and, hence, display features of a cytotoxic adaptive immune reaction and respond to ICB, whereas CMS4 tumours are marked by stromal signatures including cancer-associated fibroblasts (CAFs) and endothelial cells.122”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [122]
CMS1 tumours show a strong association with dMMR/MSI-H and display features of a cytotoxic adaptive immune reaction and respond to immune checkpoint blockade.
“CMS1 tumours show a strong association with dMMR/MSI-H and, hence, display features of a cytotoxic adaptive immune reaction and respond to ICB, whereas CMS4 tumours are marked by stromal signatures including cancer-associated fibroblasts (CAFs) and endothelial cells.122”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [122]
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.
IHC marker is named differently in the text and Figure 3
MinorThe diagnosis section names the CMS4 IHC marker HTR2B, but the Figure 3 caption lists HTRB2 for the same staining panel.
“CMS4 being defined as pMMR, CDX2-negative and FRMD6, HTR2B and ZEB1-positive tumors (28).”
“IHC staining of CDX2, FRMD6, HTRB2, and ZEB1 (28)”
Cites
The consensus molecular subtypes of colorectal cancer
Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., et al. (2015) · Nature Medicine · doi:10.1038/nm.3967 · Cited by 5,170 · see citing works
Self-citationTGFβ drives immune evasion in genetically reconstituted colon cancer metastasis
Tauriello, D. V. F., Palomo-Ponce, S., Stork, D., Berenguer-Llergo, A., Badia-Ramentol, J., Iglesias, M., Sevillano, M., Ibiza, S., Cañellas, A., Hernando-Momblona, X., et al. (2018) · Nature · doi:10.1038/nature25492 · Cited by 1,851 · see citing works
Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond
Platten, M., Nollen, E. A. A., Röhrig, U. F., Fallarino, F., & Opitz, C. A. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0016-5 · Cited by 1,586 · see citing works
Diversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265 · see citing works
Clinical and therapeutic relevance of cancer-associated fibroblasts
Chen, Y., McAndrews, K. M., & Kalluri, R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00546-5 · Cited by 1,230 · see citing works
Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis Initiation
Calon, A., Espinet, E., Palomo-Ponce, S., Tauriello, D. V. F., Iglesias, M., Céspedes, M. V., Sevillano, M., Nadal, C., Jung, P., Zhang, X. H.-F., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.08.013 · Cited by 1,060 · see citing works
Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer
Dienstmann, R., Vermeulen, L., Guinney, J., Kopetz, S., Tejpar, S., & Tabernero, J. M. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.126 · Cited by 1,038 · see citing works
TGF-β signaling in health and disease
Massagué, J., & Sheppard, D. (2023) · Cell · doi:10.1016/j.cell.2023.07.036 · Cited by 890 · see citing works
Signal Transduction Through Prion Protein
Mouillet‐Richard, S., Ermonval, M., Chebassier, C., Laplanche, J., Lehmann, S., Launay, J., & Kellermann, O. (2000) · Science · doi:10.1126/science.289.5486.1925 · Cited by 801 · see citing works
Self-citationBecht, E., de Reyniès, A., Giraldo, N. A., Pilati, C., Buttard, B., Lacroix, L., Selves, J., Sautès-Fridman, C., Laurent-Puig, P., & Fridman, W. H. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2879 · Cited by 590 · see citing works
Self-citationJoanito, I., Wirapati, P., Zhao, N., Nawaz, Z., Yeo, G., Lee, F., Eng, C. L. P., Macalinao, D. C., Kahraman, M., Srinivasan, H., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01100-4 · Cited by 434 · see citing works
Overcoming TGFβ-mediated immune evasion in cancer
Tauriello, D. V. F., Sancho, E., & Batlle, E. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-021-00413-6 · Cited by 377 · see citing works
Integrin-linked kinase – essential roles in physiology and cancer biology
McDonald, P. C., Fielding, A. B., & Dedhar, S. (2008) · Journal of Cell Science · doi:10.1242/jcs.017996 · Cited by 344 · see citing works
Isella, C., Brundu, F. G., Bellomo, S. E., Galimi, F., Zanella, E. R., Porporato, R., Petti, C., Fiori, A., Orzan, F., Senetta, R., et al. (2017) · Nature Communications · doi:10.1038/ncomms15107 · Cited by 298 · see citing works
Sirinukunwattana, K., Domingo, E., Richman, S. D., Redmond, K. L., Blake, A., Verrill, C., Leedham, S. J., Chatzipli, A., Hardy, C., Whalley, C. M., et al. (2021) · Gut · doi:10.1136/gutjnl-2019-319866 · Cited by 264 · see citing works
Sveen, A., Bruun, J., Eide, P. W., Eilertsen, I. A., Ramirez, L., Murumägi, A., Arjama, M., Danielsen, S. A., Kryeziu, K., Elez, E., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1234 · Cited by 256 · see citing works
Genetic and epigenetic characteristics of inflammatory bowel disease-associated colorectal cancer
Rajamäki, K., Taira, A., Katainen, R., Välimäki, N., Kuosmanen, A., Plaketti, R.-M., Seppälä, T. T., Ahtiainen, M., Wirta, E.-V., Vartiainen, E., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.04.042 · Cited by 230 · see citing works
ten Hoorn, S., de Back, T. R., Sommeijer, D. W., & Vermeulen, L. (2022) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djab106 · Cited by 203 · see citing works
Erratum: Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer
Dienstmann, R., Vermeulen, L., Guinney, J., Kopetz, S., Tejpar, S., & Tabernero, J. M. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.24 · Cited by 183 · see citing works
Trinh, A., Trumpi, K., De Sousa E Melo, F., Wang, X., de Jong, J. H., Fessler, E., Kuppen, P. J. K., Reimers, M. S., Swets, M., Koopman, M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0680 · Cited by 180 · see citing works
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models
Linnekamp, J. F., van Hooff, S. R., Prasetyanti, P. R., Kandimalla, R., Buikhuisen, J. Y., Fessler, E., Ramesh, P., Lee, K. A. S. T., Bochove, G. G. W., de Jong, J. H., et al. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-017-0011-5 · Cited by 177 · see citing works
De Smedt, L., Palmans, S., Andel, D., Govaere, O., Boeckx, B., Smeets, D., Galle, E., Wouters, J., Barras, D., Suffiotti, M., et al. (2017) · British Journal of Cancer · doi:10.1038/bjc.2016.382 · Cited by 163 · see citing works
TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype
Fessler, E., Drost, J., van Hooff, S. R., Linnekamp, J. F., Wang, X., Jansen, M., De Sousa E Melo, F., Prasetyanti, P. R., IJspeert, J. E., Franitza, M., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606184 · Cited by 159 · see citing works
Molecular characterization of colorectal cancer related peritoneal metastatic disease
Lenos, K. J., Bach, S., Ferreira Moreno, L., ten Hoorn, S., Sluiter, N. R., Bootsma, S., Vieira Braga, F. A., Nijman, L. E., van den Bosch, T., Miedema, D. M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32198-z · Cited by 125 · see citing works
Farin, H. F., Mosa, M. H., Ndreshkjana, B., Grebbin, B. M., Ritter, B., Menche, C., Kennel, K. B., Ziegler, P. K., Szabó, L., Bollrath, J., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0050 · Cited by 120 · see citing works
Context matters—consensus molecular subtypes of colorectal cancer as biomarkers for clinical trials
Fontana, E., Eason, K., Cervantes, A. M. R., Salazar, R., & Sadanandam, A. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz052 · Cited by 119 · see citing works
Determinants and functions of CAFs secretome during cancer progression and therapy
Linares, J., Marín-Jiménez, J. A., Badia-Ramentol, J., & Calon, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.621070 · Cited by 110 · see citing works
Linares, J., Sallent-Aragay, A., Badia-Ramentol, J., Recort-Bascuas, A., Méndez, A., Manero-Rupérez, N., Re, D. L., Rivas, E. I., Guiu, M., Zwick, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36334-1 · Cited by 109 · see citing works
Dunne, P. D., Alderdice, M., O'Reilly, P. G., Roddy, A. C., McCorry, A. M. B., Richman, S., Maughan, T., McDade, S. S., Johnston, P. G., Longley, D. B., et al. (2017) · Nature Communications · doi:10.1038/ncomms15657 · Cited by 94 · see citing works
Kawazoe, A., Kuboki, Y., Shinozaki, E., Hara, H., Nishina, T., Komatsu, Y., Yuki, S., Wakabayashi, M., Nomura, S., Sato, A., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-1803 · Cited by 93 · see citing works
AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer
Varga, J., Nicolas, A. M., Petrocelli, V., Pesic, M. H., Mahmoud, A., Michels, B. E., Etlioglu, E., Yepes, D., Häupl, B., Ziegler, P. K., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191515 · Cited by 93 · see citing works
Consensus molecular subtype classification of colorectal adenomas
Komor, M. A., Bosch, L. J., Bounova, G., Bolijn, A. S., Delis‐van Diemen, P. M., Rausch, C., Hoogstrate, Y., Stubbs, A. P., de Jong, M., Jenster, G., et al. (2018) · The Journal of Pathology · doi:10.1002/path.5129 · Cited by 86 · see citing works
Trinh, A., Lädrach, C., Dawson, H. E., ten Hoorn, S., Kuppen, P. J. K., Reimers, M. S., Koopman, M., Punt, C. J. A., Lugli, A., Vermeulen, L., et al. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0230-7 · Cited by 83 · see citing works
Back to the Colorectal Cancer Consensus Molecular Subtype Future
Menter, D. G., Davis, J. S., Broom, B. M., Overman, M. J., Morris, J. S., & Kopetz, S. (2019) · Current Gastroenterology Reports · doi:10.1007/s11894-019-0674-9 · Cited by 81 · see citing works
Adipose stem cell niche reprograms the colorectal cancer stem cell metastatic machinery
Di Franco, S., Bianca, P., Sardina, D. S., Turdo, A., Gaggianesi, M., Veschi, V., Nicotra, A., Mangiapane, L. R., Lo Iacono, M., Pillitteri, I., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25333-9 · Cited by 80 · see citing works
Sequence of molecular genetic events in colorectal tumorigenesis
Laurent‐Puig, P., Bons, H., & Cugnenc, P. (1999) · European Journal of Cancer Prevention · doi:10.1097/00008469-199912001-00007 · Cited by 78 · see citing works
Self-citationMicroRNA–mRNA interactions underlying colorectal cancer molecular subtypes
Cantini, L., Isella, C., Petti, C., Picco, G., Chiola, S., Ficarra, E., Caselle, M., & Médico, E. (2015) · Nature Communications · doi:10.1038/ncomms9878 · Cited by 76 · see citing works
Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer
Eide, P. W., Moosavi, S. H., Eilertsen, I. A., Brunsell, T. H., Langerud, J., Berg, K. C. G., Røsok, B. I., Bjørnbeth, B. A., Nesbakken, A., Lothe, R. A., et al. (2021) · npj Genomic Medicine · doi:10.1038/s41525-021-00223-7 · Cited by 70 · see citing works
Intratumor CMS heterogeneity impacts patient prognosis in localized colon cancer
Marisa, L., Blum, Y., Taieb, J., Ayadi, M., Pilati, C., Le Malicot, K., Lepage, C., Salazar, R., Aust, D., Duval, A., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0529 · Cited by 68 · see citing works
Self-citationZeb2 drives invasive and microbiota-dependent colon carcinoma
Slowicka, K., Πέττα, Ι., Blancke, G., Hoste, E., Dumas, E., Sze, M., Vikkula, H., Radaelli, E., Haigh, J. J., Jonckheere, S., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0070-2 · Cited by 63 · see citing works
Piskol, R., Huw, L., Sergin, I., Kljin, C., Modrusan, Z., Kim, D., Kljavin, N., Tam, R., Patel, R., Burton, J., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3032 · Cited by 62 · see citing works
Martínez-Ordóñez, A., Durán, Á., Ruíz-Martínez, M., Cid-Diaz, T., Zhang, X., Han, Q., Kinoshita, H., Muta, Y., Linares, J. F., Kasashima, H., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.11.016 · Cited by 60 · see citing works
Co-migration of colon cancer cells and CAFs induced by TGFβ₁ enhances liver metastasis
Gonzalez-Zubeldia, I., Dotor, J., Redrado, M., Bleau, A.-M., Manrique, I., de Aberasturi, A. L., Villalba, M., & Calvo, A. (2015) · Cell and Tissue Research · doi:10.1007/s00441-014-2075-6 · Cited by 51 · see citing works
Colorectal premalignancy is associated with consensus molecular subtypes 1 and 2
Chang, K., Willis, J. A., Reumers, J., Taggart, M. W., San Lucas, F. A., Thirumurthi, S., Kanth, P., Delker, D. A., Hagedorn, C. H., Lynch, P. M., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy337 · Cited by 51 · see citing works
Le Corre, D., Ghazi, A., Balogoun, R., Pilati, C., Aparicio, T., Martin-Lannerée, S., Marisa, L., Djouadi, F., Poindessous, V., Crozet, C., et al. (2019) · eBioMedicine · doi:10.1016/j.ebiom.2019.07.036 · Cited by 48 · see citing works
Self-citationOrouji, E., Raman, A. T., Singh, A., Sorokin, A., Arslan, E., Ghosh, A. K., Schulz, J., Terranova, C. J., Jiang, S., Tang, M., et al. (2020) · Gut · doi:10.1136/gutjnl-2020-322835 · Cited by 48 · see citing works
Basile, D., Broudin, C., Emile, J. F., Falcoz, A., Pagès, F., Mineur, L., Bennouna, J., Louvet, C., Artru, P., Fratte, S., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.03.002 · Cited by 47 · see citing works
Neoadjuvant chemotherapy affects molecular classification of colorectal tumors
Trumpi, K., Ubink, I., Trinh, A., Djafarihamedani, M., Jongen, J. M., Govaert, K. M., Elias, S. G., van Hooff, S. R., Medema, J. P., Lacle, M. M., et al. (2017) · Oncogenesis · doi:10.1038/oncsis.2017.48 · Cited by 46 · see citing works
Ubink, I., Elias, S. G., Moelans, C. B., Laclé, M. M., van Grevenstein, W. M. U., van Diest, P. J., Borel Rinkes, I. H. M., & Kranenburg, O. (2017) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djw303 · Cited by 40 · see citing works
YAP/TAZ signalling in colorectal cancer: lessons from consensus molecular subtypes
Mouillet-Richard, S., & Laurent-Puig, P. (2020) · Cancers · doi:10.3390/cancers12113160 · Cited by 40 · see citing works
Self-citationMorris, V. K., Overman, M. J., Lam, M., Parseghian, C. M., Johnson, B., Dasari, A., Raghav, K., Kee, B. K., Huey, R., Wolff, R. A., et al. (2022) · Cancer Research Communications · doi:10.1158/2767-9764.crc-22-0194 · Cited by 38 · see citing works
Morris, J. S., Luthra, R., Liu, Y., Duose, D. Y., Lee, W., Reddy, N. G., Windham, J., Chen, H., Tong, Z., Zhang, B., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2403 · Cited by 36 · see citing works
Strating, E., Wassenaar, E., Verhagen, M., Rauwerdink, P., van Schelven, S., de Hingh, I., Rinkes, I. B., Boerma, D., Witkamp, A., Lacle, M., et al. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01748-z · Cited by 36 · see citing works
Peters, N. A., Constantinides, A., Ubink, I., van Kuik, J., Bloemendal, H. J., van Dodewaard, J. M., Brink, M. A., Schwartz, T. P., Lolkema, M. P. J. K., Lacle, M. M., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.969855 · Cited by 35 · see citing works
Cyclin A2 maintains colon homeostasis and is a prognostic factor in colorectal cancer
Guo, Y., Gabola, M., Lattanzio, R., Paul, C., Pinet, V., Tang, R., Turali, H., Bremond, J., Longobardi, C., Maurizy, C., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci131517 · Cited by 33 · see citing works
Buikhuisen, J. Y., Gomez Barila, P. M., Torang, A., Dekker, D., de Jong, J. H., Cameron, K., Vitale, S., Stassi, G., van Hooff, S. R., Castro, M. A. A., et al. (2021) · Cancers · doi:10.3390/cancers13040801 · Cited by 33 · see citing works
Källberg, J., Harrison, A., March, V., Bērziņa, S., Nemazanyy, I., Kepp, O., Kroemer, G., Mouillet‐Richard, S., Laurent‐Puig, P., Taly, V., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05806-z · Cited by 31 · see citing works
Self-citationHaasnoot, K. J. C., Backes, Y., Moons, L. M. G., Kranenburg, O., Trinh, A., Vermeulen, L., Noë, M., Tuynman, J. B., van Lent, A. U. G., van Ginneken, R., et al. (2020) · Modern Pathology · doi:10.1038/s41379-020-0598-9 · Cited by 30 · see citing works
Jongen, J. M. J., van der Waals, L. M., Trumpi, K., Laoukili, J., Peters, N. A., van Schelven, S. J., Govaert, K. M., Rinkes, I. H. M. B., & Kranenburg, O. (2017) · Oncotarget · doi:10.18632/oncotarget.21145 · Cited by 27 · see citing works
Interconnectivity between molecular subtypes and tumor stage in colorectal cancer
Coebergh van den Braak, R. R. J., ten Hoorn, S., Sieuwerts, A. M., Tuynman, J. B., Smid, M., Wilting, S. M., Martens, J. W. M., Punt, C. J. A., Foekens, J. A., Medema, J. P., et al. (2020) · BMC Cancer · doi:10.1186/s12885-020-07316-z · Cited by 27 · see citing works
The Cellular Prion Protein and the Hallmarks of Cancer
Mouillet‐Richard, S., Ghazi, A., & Laurent‐Puig, P. (2021) · Cancers · doi:10.3390/cancers13195032 · Cited by 27 · see citing works
Self-citationTeufel, M., Schwenke, S., Seidel, H., Beckmann, G., Reischl, J., Vonk, R., Lenz, H.-J., Tabernero, J., Siena, S., Grothey, A., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.3558 · Cited by 26 · see citing works
Xu, T., Verhagen, M., Joosten, R., Sun, W., Sacchetti, A., Munoz Sagredo, L., Orian-Rousseau, V., & Fodde, R. (2022) · eLife · doi:10.7554/elife.82006 · Cited by 25 · see citing works
MmCMS: mouse models’ consensus molecular subtypes of colorectal cancer
Amirkhah, R., Gilroy, K. L., Malla, S. B., Lannagan, T. R. M., Byrne, R. M., Fisher, N. C., Corry, S. M., Mohamed, N.-E., Naderi‐Meshkin, H., Mills, M. L., et al. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02157-6 · Cited by 24 · see citing works
Bastin, J., Sroussi, M., Nemazanyy, I., Laurent-Puig, P., Mouillet-Richard, S., & Djouadi, F. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04341-x · Cited by 24 · see citing works
Self-citationYang, M., Davis, T. B., Pflieger, L., Nebozhyn, M. V., Loboda, A., Wang, H., Schell, M. J., Thota, R., Pledger, W. J., & Yeatman, T. J. (2022) · BMC Cancer · doi:10.1186/s12885-022-09344-3 · Cited by 22 · cited 1× · see citing works
“From gene expression signatures studies, KRAS -mutated CMS4colorectal cancer was further predicted to respond to combined MEK and SRC inhibition (69).”
BackgroundMimoun, S. B., & Mauviel, A. (2018) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2018.03.006 · Cited by 21 · see citing works
Prognostic value of the PrP <sup>C</sup> -ILK-IDO1 axis in the mesenchymal colorectal cancer subtype
Ghazi, A., Le Corre, D., Pilati, C., Taieb, J., Aparicio, T., Didelot, A., Dedhar, S., Mulot, C., Le Malicot, K., Djouadi, F., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1940674 · Cited by 21 · see citing works
Self-citationLenz, H., Argilés, G., Yoshino, T., Tejpar, S., Ciardiello, F., Braunger, J., Salnikov, A. V., Gabrielyan, O., Schmid, R., Höfler, J., et al. (2020) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2020.09.003 · Cited by 18 · see citing works
Corry, S. M., McCorry, A. M., Lannagan, T. R., Leonard, N. A., Fisher, N. C., Byrne, R. M., Tsantoulis, P., Cortes-Lavaud, X., Amirkhah, R., Redmond, K. L., et al. (2022) · Gut · doi:10.1136/gutjnl-2021-326183 · Cited by 18 · see citing works
Küçükköse, E., Peters, N. A., Ubink, I., van Keulen, V. A. M., Daghighian, R., Verheem, A., Laoukili, J., & Kranenburg, O. (2022) · Cell Death & Disease · doi:10.1038/s41419-022-05078-z · Cited by 18 · see citing works
Stahler, A., Hoppe, B., Na, I.-K., Keilholz, L., Müller, L., Karthaus, M., Fruehauf, S., Graeven, U., Fischer von Weikersthal, L., Goekkurt, E., et al. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.22.02582 · Cited by 16 · see citing works
Mouillet-Richard, S., Martin-Lannerée, S., Le Corre, D., Hirsch, T. Z., Ghazi, A., Sroussi, M., Pilati, C., de Reyniès, A., Djouadi, F., Vodovar, N., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02430-7 · Cited by 14 · see citing works
Self-citationToledano‐Fonseca, M., Gómez‐España, M. A., Élez, E., Grávalos, C., Alfonso, P. G., Rodríguez, R., Losa, F., Díaz, I. A., Graña, B., Valladares‐Ayerbes, M., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114272 · Cited by 9 · see citing works
Buikhuisen, J. Y., Barila, P. M. G., Cameron, K., Suijkerbuijk, S. J. E., Lieftink, C., Franco, S. D., García, A. K., Uceda-Castro, R., Lenos, K., Nijman, L. E., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02600-9 · Cited by 9 · see citing works
Consensus molecular subtype transition during progression of colorectal cancer
van de Weerd, S., Torang, A., Zwager, L. W., Koelink, P. J., Koster, J., Bastiaansen, B. A., Lammers, V., Longobardi, C., Roodhart, J. M., van Krieken, J. H., et al. (2023) · The Journal of Pathology · doi:10.1002/path.6176 · Cited by 6 · see citing works
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Obesity-Associated Colorectal Cancer
Gonzalez-Gutierrez, L., Motiño, O., Barriuso, D., de la Puente-Aldea, J., Alvarez-Frutos, L., Kroemer, G., Palacios, R., & Senovilla, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168836 · Cited by 51 · see citing works
Current and emerging concepts for systemic treatment of metastatic colorectal cancer
Steup, C., Kennel, K. B., Neurath, M. F., Fichtner-Feigl, S., & Greten, F. R. (2025) · Gut · doi:10.1136/gutjnl-2025-335412 · Cited by 39 · see citing works
Polyclonality overcomes fitness barriers in Apc-driven tumorigenesis
Sadien, I. D., Adler, S., Mehmed, S., Bailey, S., Sawle, A., Couturier, D., Eldridge, M., Adams, D. J., Kemp, R., Lourenço, F. C., et al. (2024) · Nature · doi:10.1038/s41586-024-08053-0 · Cited by 30 · see citing works
Recent advances and challenges in colorectal cancer: From molecular research to treatment
Qi, G., Zhao, R., Gao, C., Ma, Z., Wang, S., & Xu, J. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i21.106964 · Cited by 31 · see citing works
Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts
Flynn, J. M., Thadani, N., Gallagher, E. E., Azzaro, I., Bodnar, C. M., McCarty, C. P., Romano, G., Webster, M. R., & Capparelli, C. (2025) · Cancer Research · doi:10.1158/0008-5472.can-24-3037 · Cited by 30 · see citing works
O’Neill, A., Zakaria, N., Egan, H., Corry, S. M., Bull, C., Leonard, N. A., O'Meara, C., Howard, L., Walsh, A., Reidy, E., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-012491 · Cited by 14 · see citing works
Keivany, M. R., Asrami, E. S., Besharatloo, M., Latifi, H., & Barjasteh, A. H. (2026) · Cancer Cell International · doi:10.1186/s12935-026-04177-7 · Cited by 14 · see citing works
Agostino, S. D., Padula, D. L., Rago, V., Gabriele, C., Conforti, F., Aprigliano, E., Urlandini, L., Parrotta, E. I., Lofaro, D., Vescio, F., et al. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03496-3 · Cited by 10 · see citing works
Tête, A., Debizet, K., Rives, C., Imler, J., Safi-Stibler, S., Gales, L., Bellvert, F., Dairou, J., Hagimont, A., Burel, A., et al. (2025) · Environment International · doi:10.1016/j.envint.2025.109503 · Cited by 7 · see citing works
Self-citationMa, M., Chu, J., Zhuo, C., Xiong, X., Gu, W., Li, H., Xu, M., & Huang, D. (2025) · APOPTOSIS · doi:10.1007/s10495-024-02063-z · Cited by 7 · see citing works
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Toews, K. P., Auld, F. M., & Moyana, T. N. (2025) · Pathophysiology · doi:10.3390/pathophysiology32040052 · Cited by 5 · see citing works
Bacteroides fragilis Promotes Mesenchymal Subtype in Colorectal Cancer
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Research status of colorectal cancer treatment based on natural killer cell immunotherapy
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Decoding colorectal cancer targeted therapy: a bibliometric journey of the last decade (2015–2024)
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Ke, J., Li, Y., Qi, L., Li, X., Wang, W., ten Hoorn, S., Zhu, Y., Huang, H., Gao, F., Vermeulen, L., et al. (2025) · ESMO Gastrointestinal Oncology · doi:10.1016/j.esmogo.2025.100181 · Cited by 4 · see citing works
Gandini, A., Gallois, C., Blons, H., Mulot, C., Agueeff, N., Lepage, C., Guimbaud, R., Mineur, L., Desrame, J., Chibaudel, B., et al. (2024) · ESMO Gastrointestinal Oncology · doi:10.1016/j.esmogo.2024.100106 · Cited by 4 · see citing works
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Shimpi, A. N., Sonawane, Y. D., & Bhattacharya, S. (2025) · Nanotechnology · doi:10.1088/1361-6528/ae2a3d · Cited by 2 · see citing works
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Okotel, M., & Huang, C. (2025) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2025060830 · Cited by 1 · see citing works
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Biophysical approaches to cancer diagnostics: Collagen biomarkers in colorectal cancer
Biswas, S., & Mahato, K. K. (2026) · Physics of Life Reviews · doi:10.1016/j.plrev.2026.01.009 · Cited by 1 · see citing works
NICD3 mediates pro-angiogenic effects through SMAD3/TGFBI axis in colorectal cancer
An, R., Yu, R., Wen, X., Ma, Q., Mao, K., Zhang, Q., Mao, L., Feng, X., Xin, F., Liu, P., et al. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08939-z · Cited by 1 · see citing works
Ju, K., Liu, X., Wang, Q., Liu, X., Li, D., & Tan, B. (2025) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16985 · Cited by 1 · see citing works
Qiu, A., Lu, B., Cooper, G. F., Lu, X., & Chen, L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.20.677543
Äijälä, V. K., Härkönen, J., Sirniö, P., Mantere, T., Elomaa, H., Sirkiä, O., Kehusmaa, A., Karjalainen, H., Kastinen, M., Tapiainen, V. V., et al. (2025) · British Journal of Cancer · doi:10.1038/s41416-025-03300-1
Jiang, T., Zhu, S., Zhou, H., Zhang, N., Zhang, L., Zou, C., & Song, H. (2026) · Cancer Informatics · doi:10.1177/11769351251412614
Guo, Z., & (405), W. Z. (2026) · Molecular Genetics and Genomics · doi:10.1007/s00438-026-02377-4
Zhou, Z., Ferlita, A. L., Palavalli, M. H., Chen, X., Tyler, L. A., Ejaz, A. M., Beane, J. D., Polanco, P. M., Huang, H., & Kim, A. C. (2026) · Oncogene · doi:10.1038/s41388-026-03743-7
Hayashishita, S., Okayama, H., Nakajima, S., Saito, K., Takiguchi, C., Mitsui, D., Matsuida, H., Katagata, M., Sato, T., Matsumoto, T., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-57104-1
Guoyu-Li, Xudong-Yang, Qing-Feng, Enshan-Zhu, Lixing-Zhang, Rong-Ding, Xuan-Zhang, Xiaoqiong-Chen, & Yunfeng-Li (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112745
Ganguly, D., GHOSH, S., Deka, H., Sarmah, J., Majumdar, S., Mahanti, K., Hoque, N., & Ghosh, S. (2026) · Clinical & Translational Oncology · doi:10.1007/s12094-026-04516-0
Kasai, S., Hatakeyama, K., Shiomi, A., Hotta, K., Manabe, S., Imai, K., Tanaka, Y., Kojima, T., Ohshima, K., Urakami, K., et al. (2026) · Journal of the Anus Rectum and Colon · doi:10.23922/jarc.2026-004
Deciphering the colorectal tumor microenvironment: Interactions and targets for effective therapy
Zhao, J., Shi, C., Du, Y., Li, G., & Yan, C. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118303
Xing, K., Li, L., Feng, S., Yang, T., He, Y., Ma, Y., Luo, W., & Zhu, J. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177659
Undurraga, M., Lang, N., Koessler, T., Diciolla, A., Marco, M. D., Mach, N., Raimond, C., Genoud, V., Bois, V. D., Tille, J., et al. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106477
ADORA1 inhibition suppresses colon cancer development via hippo tumor suppressor pathway
Li, Z., Liu, Z., Zhang, X., Bao, Z., Cui, X., Li, X., Cui, J., Shen, F., Zhou, Y., Song, P., et al. (2026) · Cell Death and Differentiation · doi:10.1038/s41418-026-01860-0
Wan, K., Tang, K., Wang, L., Tian, Q., Zheng, M., Qian, C., & 刘丽梅 (2026) · MedComm · doi:10.1002/mco2.71028
Mo, H., Han, H., O'Dwyer, M. E., Reidy, E., & Ryan, A. E. (2026) · The Journal of Physiology · doi:10.1113/jp291166
Tomuț, A. N., Cozac-Szőke, A. R., Szász, E. A., Tinca, A. C., Sabău, A.-H., Cocuz, I. G., Chiorean, D. M., & Cotoi, O. S. (2026) · Immuno · doi:10.3390/immuno6040067
- Authors
- Mouillet-Richard, S., Cazelles, A., Sroussi, M., Gallois, C., Taieb, J., & Laurent-Puig, P.
- Affiliations
- 1Team “Personalized medicine, pharmacogenomics, therapeutic optimization”, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France.
- Inserm (FR)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2024-04-02
- Volume
- 30
- Issue
- 11
- Pages
- 2351-2358
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC11145159
- OpenAlex
- W4393537476
- Semantic Scholar
- e55354842ab1197c9eb56a159d90d202bc65ac1a
- Cited by
- 43
- References
- 76
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 3
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Cancer Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Funders
- SIRIC CARPEM (INCa-DGOS-INSERM-ITMO Cancer_18006)
- Fondation ARCAD
- Labex Immuno-oncology
- Association pour la Recherche sur le Cancer
- Cancéropôle Ile de France
- Fondation pour la Recherche Médicale
- Institut National Du Cancer
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- colorectal cancer, precision medicine, tumor microenvironment, prognostic factors, treatment challenges, molecular pathways, diagnostic biomarkers, preclinical models, tailored treatment
- MeSH terms
- Colonic Neoplasms, Humans, Prognosis, Biomarkers, Tumor, Colorectal Neoplasms, Consensus Sequence, Precision Medicine, Molecular Targeted Therapy, 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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
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.
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