Development of molecularly targeted therapies in biliary tract cancers: Reassessing the challenges and opportunities

Authors

  • Andrew X. Zhu,

    Corresponding author
    1. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
    • Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston MA 02114
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    • fax: (617) 724-3166

  • Aram F. Hezel

    1. James P. Wilmot Cancer Center, University of Rochester School of Medicine, Rochester, NY
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  • Potential conflict of interest: Dr. Zhu advises Novartis, Pfizer, and Bayer. Dr. Hezel serves on the speaker's bureau of Augen and Bayer and receives grants from Augen.

Abstract

Biliary tract cancers (BTCs), which encompass intra- and extrahepatic cholangiocarcinomas as well as gallbladder carcinomas, are a genetically diverse collection of cancers. Most patients with BTC will present with unresectable or metastatic disease. Although the standard systemic chemotherapy approaches are emerging, the prognosis remains poor. Development of molecularly targeted therapies in advanced BTC remains challenging. Recent early-stage clinical trials with targeted therapies appear promising, although the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. Here we summarize the relevant molecular pathogenesis, recent and ongoing clinical trials with targeted agents, and the key issues in clinical trial design in BTC. (HEPATOLOGY 2011;53:695-704)

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