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 Feiler, Andrew H. Ko, Adam B. Olshen, Kathleen L. Danenberg, Margaret A. Tempero, Paul Spellman, Douglas Hanahan, Joe Gray

Research output: Contribution to journalArticle

533 Citations (Scopus)

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

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Tumors
Adenocarcinoma
Neoplasms
Therapeutics
Genes
Cells
Drug Delivery Systems
Lung Neoplasms
Breast Neoplasms
Cell Line
Survival
Population

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Collisson, E. A., Sadanandam, A., Olson, P., Gibb, W. J., Truitt, M., Gu, S., ... Gray, J. (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

Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. / 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; Ko, Andrew H.; Olshen, Adam B.; Danenberg, Kathleen L.; Tempero, Margaret A.; Spellman, Paul; Hanahan, Douglas; Gray, Joe.

In: Nature Medicine, Vol. 17, No. 4, 04.2011, p. 500-503.

Research output: Contribution to journalArticle

Collisson, EA, Sadanandam, A, Olson, P, Gibb, WJ, Truitt, M, Gu, S, Cooc, J, Weinkle, J, Kim, GE, Jakkula, L, Feiler, H, Ko, AH, Olshen, AB, Danenberg, KL, Tempero, MA, Spellman, P, Hanahan, D & Gray, J 2011, 'Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy', Nature Medicine, vol. 17, no. 4, pp. 500-503. https://doi.org/10.1038/nm.2344
Collisson EA, Sadanandam A, Olson P, Gibb WJ, Truitt M, Gu S et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nature Medicine. 2011 Apr;17(4):500-503. https://doi.org/10.1038/nm.2344
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 ; Ko, Andrew H. ; Olshen, Adam B. ; Danenberg, Kathleen L. ; Tempero, Margaret A. ; Spellman, Paul ; Hanahan, Douglas ; Gray, Joe. / Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. In: Nature Medicine. 2011 ; Vol. 17, No. 4. pp. 500-503.
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