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Pancreatic cancer subtypes: a roadmap for precision medicine
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cause of cancer-related deaths by 2020. Although it has traditionally been approached as a disease, accumulated evidences point to the clinical heterogeneity of this disease, which translate into disparity in outcomes among the patients. Much emphasis has been put into patient classification introducing a platform for more tailored therapies. In the last 10 years, there have been important advances in the understanding of the molecular pathogenesis of PDAC, which has culminated with a comprehensive integrated genomic analysis from RNA expression profiles. Bailey et al. defined four subtypes and the different transcriptional networks underlying them. Firstly, we briefly describe and compare different subtyping approaches, which are mostly based on tissue mRNA expression analysis. We propose that these latest approaches to disease classification embrace not only those patients that are surgically resectable (20%), but even patients ineligible for surgery. Such considerations will include possible reclassification of these specific subtypes, enabling more personalized diagnosis and individualized treatment. The ultimate goal of this review is to identify current challenges in this area and summarize current efforts in developing clinical modalities that can effectively identify these subtypes in order to advance Precision Medicine. KEY MESSAGES • Pancreatic cancer can no longer be considered as one disease. • The heterogeneity underlying pancreatic cancer patients makes therapeutic options based on one-size-fits-all approach ineffective. • Identifying patients that could benefit from a specific treatment would help to avoid futile therapy approaches and to improve outcomes and quality of life of those whose long-term survival is unpromising.
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“primary tumors have been shown to undergo subtype switching in response to microenvironmental cues (Torres 2018)37.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as Torres 2018
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“primary tumors have been shown to undergo subtype switching in response to microenvironmental cues (Torres 2018)37.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as [37]
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“Both cancer types are highly heterogeneous diseases characterized by diverse molecular and morphological features with the quasi-mesenchymal/squamous subtype of human PDAC [5] or basal-like subtype of BC [6] having the worst prognosis of any of the recently identified subtypes.”
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“Although there have been some advances in precision medicine strategies for pancreas cancer, there are currently few targets for precision medicine in pancreatic tumors [33,34].”
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“Previous studies have already investigated the molecular classification and the internal heterogeneity of pancreatic cancer using omics data [9, 10].”
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Salvia, A. L., Persano, I., Parlagreco, E., Audisio, A., Cani, M., & Brizzi, M. P. (2022) · Medical Oncology · doi:10.1007/s12032-022-01764-2 · Cited by 8
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“Others still recommend profiling the tumor tissue of all pati nts coming in with PDAC [75] wit the recent Natio al Compre ensive Cancer Network (NCCN) guidelines for PDAC strongly recommending molecular tumor analysis [64].”
BackgroundThe road to overcome pancreatic cancer: Where are we?
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“The response of PDAC to chemotherapy is in fl uenced by their subtypes; quasi-mesenchymal was shown to be more sensitive to gemcitabine while erlotinib was more effective in classical PDAC cell lines (Torres and Grippo, 2018).”
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Metadata
- Authors
- Torres, C., & Grippo, P. J.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Torres, Carolina
- Venue
- Annals of Medicine
- Publisher
- Informa UK Limited
- Published
- 2018-03-22
- Volume
- 50
- Issue
- 4
- Pages
- 277-287
- ISSN
- 0785-3890 (ISSN-L)
- 1365-2060
- PMC
- PMC6151873
- OpenAlex
- W2793975714
- Cited by
- 104
- References
- 54
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 11 · 2023: 16 · 2022: 21 · 2021: 20 · 2020: 9 · 2019: 7 · 2018: 2
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (1R01CA161283)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- pancreatic ductal adenocarcinoma, tumor subtypes, molecular classification, precision medicine, RNA expression profiling, tumor heterogeneity, personalized treatment, resectability, unresectable pancreatic cancer
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Clinical Trials as Topic, Humans, Pancreas, Pancreatectomy, Pancreatic Neoplasms, Prognosis, RNA, Messenger, Biomarkers, Tumor, Treatment Outcome, Patient Selection, Drug Resistance, Neoplasm, Gene Expression Profiling, Carcinoma, Pancreatic Ductal, Genomics, Precision Medicine, Molecular Targeted Therapy
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