Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy

胰腺导管腺癌 医学 肿瘤科 腺癌 临床试验 胰腺癌 疾病 内科学 生物信息学 癌症研究 癌症 生物
作者
Eric A. Collisson,Anguraj Sadanandam,Peter Olson,William J. Gibb,Morgan Truitt,Shenda Gu,J. Cooc,Jennifer Weinkle,Grace Kim,Lakshmi R. Jakkula,Heidi S. Feiler,Andrew H. Ko,Adam B. Olshen,Kathleen L Danenberg,Margaret A. Tempero,Paul T. Spellman,Douglas Hanahan,Joe W. Gray
出处
期刊:Nature Medicine [Springer Nature]
卷期号:17 (4): 500-503 被引量:1585
标识
DOI:10.1038/nm.2344
摘要

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 diagnosis1. 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 breast2 and lung3 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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