Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy

Eric A. Collisson, Anguraj Sadanandam, Peter Olson, William J. Gibb, Morgan Truitt, Shenda Gu, Janine Cooc, Jennifer Weinkle, Grace E. Kim, Lakshmi Jakkula, Heidi S. Feiler, Andrew H. Ko, Adam B. Olshen, Kathleen L. Danenberg, Margaret A. Tempero, Paul T. Spellman, Douglas Hanahan, Joe W. Gray

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616 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)500-503
Number of pages4
JournalNature medicine
Volume17
Issue number4
DOIs
StatePublished - Apr 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    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. (2011). Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nature medicine, 17(4), 500-503. https://doi.org/10.1038/nm.2344