Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDA) is a lethal disease. Overall survival is typically 6 months from diagnosis. Numerous phase 3 trials of agents effective in other malignancies have failed to benefit unselected PDA populations, although patients do occasionally respond. Studies in other solid tumors have shown that heterogeneity in response is determined, in part, by molecular differences between tumors. Furthermore, treatment outcomes are improved by targeting drugs to tumor subtypes in which they are selectively effective, with breast and lung cancers providing recent examples. Identification of PDA molecular subtypes has been frustrated by a paucity of tumor specimens available for study. We have overcome this problem by combined analysis of transcriptional profiles of primary PDA samples from several studies, along with human and mouse PDA cell lines. We define three PDA subtypes: classical, quasimesenchymal and exocrine-like, and we present evidence for clinical outcome and therapeutic response differences between them. We further define gene signatures for these subtypes that may have utility in stratifying patients for treatment and present preclinical model systems that may be used to identify new subtype specific therapies.
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Collisson, Sadanandam and colleagues identified three PDAC subtypes-classical, quasimesenchymal, and exocrine-like-using patient microarray datasets and PDAC cell lines.
“They identified three subtypes, termed “classical”, “quasimesenchymal”, and “exocrine-like”130.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [130]
These three subtypes could predict drug response in cell culture models, and patient outcomes differed significantly across subtypes.
“these subtypes could predict drug response in cell culture models, and patient outcomes were significantly different across their subtypes.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [130]
The glycolytic metabolic subtype aligns with a quasimesenchymal transcriptional subtype, and the lipogenic metabolic state aligns with a classical signature.
“The glycolytic metabolic subtype aligns with a “quasimesenchymal” transcriptional subtype and lipogenic metabolism state with a “classical” signature130.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [130]
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- Authors
- Collisson, E. A., Sadanandam, A., Olson, P., Gibb, W. J., Truitt, M., Gu, S., Cooc, J., Weinkle, J., Kim, G. E., Jakkula, L., Feiler, H. S., Ko, A. H., Olshen, A. B., Danenberg, K. L., Tempero, M. A., Spellman, P. T., Hanahan, D., & Gray, J. W.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- University of California, San Francisco (US)
- Corresponding author
- Gray, Joe W
- ORCID
- Venue
- Nature Medicine
- Published
- 2011-04
- Volume
- 17
- Issue
- 4
- Pages
- 500-503
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC3755490
- OpenAlex
- W2154790710
- Cited by
- 1,967
- References
- 39
- Citations by year
- 2026: 142 · 2025: 155 · 2024: 163 · 2023: 200 · 2022: 215 · 2021: 221 · 2020: 193 · 2019: 146 · 2018: 121 · 2017: 109 · 2016: 90 · 2015: 64 · 2014: 46 · 2013: 46 · 2012: 39
- FWCI
- 22.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Cancer Institute (K08CA137153, P50CA058207, P50CA083639, P01CA117969, U54CA112970)
- 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, classical subtype, gene expression signatures, gene expression profiling, treatment response, prognosis, molecular heterogeneity
- MeSH terms
- Erlotinib Hydrochloride, Gemcitabine, Animals, Antineoplastic Agents, Deoxycytidine, Female, Humans, Male, Pancreatic Neoplasms, Pharmacogenetics, Proto-Oncogene Proteins, Quinazolines, Proto-Oncogene Proteins p21(ras), ras Proteins, Gene Expression Profiling, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, GATA6 Transcription Factor, Mice
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