Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy

This report describes the identification of three molecularly distinct subtypes of pancreatic ductal adenocarninoma (PDA). The classical, quasimesenchymal and exocrine subtypes can further stratify tumors with the same genetic alterations, and could be useful to improve prognosis and predict treatme...

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Bibliographic Details
Published in:	Nature medicine Vol. 17; no. 4; pp. 500 - 503
Main Authors:	Collisson, Eric A, Sadanandam, Anguraj, Olson, Peter, Gibb, William J, Truitt, Morgan, Gu, Shenda, Cooc, Janine, Weinkle, Jennifer, Kim, Grace E, Jakkula, Lakshmi, Feiler, Heidi S, Ko, Andrew H, Olshen, Adam B, Danenberg, Kathleen L, Tempero, Margaret A, Spellman, Paul T, Hanahan, Douglas, Gray, Joe W
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-04-2011 Nature Publishing Group
Subjects:	631/1647/2217/2018 631/67/1059 692/308 692/699/67/1504/1713 Adenocarcinoma Animals Antineoplastic Agents - pharmacology Biomedical and Life Sciences Biomedicine Cancer Cancer Research Carcinoma, Pancreatic Ductal - classification Carcinoma, Pancreatic Ductal - drug therapy Carcinoma, Pancreatic Ductal - genetics Care and treatment Cell Line, Tumor Cellular biology Chemotherapy Deoxycytidine - analogs & derivatives Deoxycytidine - pharmacology Diagnosis Erlotinib Hydrochloride Female GATA6 Transcription Factor - genetics Gene expression Gene Expression Profiling Heterogeneity Humans Infectious Diseases letter Male Metabolic Diseases Mice Molecular biology Molecular Medicine Neurosciences Pancreatic cancer Pancreatic Neoplasms - classification Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - genetics Personal digital assistants Pharmacogenetics Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins p21(ras) Quinazolines - pharmacology ras Proteins - genetics Tumors United States
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Summary:	This report describes the identification of three molecularly distinct subtypes of pancreatic ductal adenocarninoma (PDA). The classical, quasimesenchymal and exocrine subtypes can further stratify tumors with the same genetic alterations, and could be useful to improve prognosis and predict treatment response. Pancreatic ductal adenocarcinoma (PDA) is a lethal disease. Overall survival is typically 6 months from diagnosis 1 . 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 2 and lung 3 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.
Bibliography:	Current Address: Pfizer, 10724 Science Center Drive, La Jolla, CA 92121 Current Address: Genomic Health, 301 Penobscot Drive, Redwood City, CA 94063 Equal Contributors
ISSN:	1078-8956 1546-170X
DOI:	10.1038/nm.2344