Precision Medicine in Biliary Tract Cancers: Actionable Mutations and Emerging Targeted Therapies
This review surveys the molecular landscape of biliary tract cancers, where NGS profiling has identified actionable alterations including FGFR fusions and IDH1/2 mutations. The authors trace the evolution from unsuccessful EGFR/angiogenesis trials to encouraging results with mutation-targeted agents now entering clinical development. For diagnostic laboratories, the findings underscore the importance of comprehensive genomic profiling in cholangiocarcinoma and gallbladder cancer to identify patients eligible for emerging targeted therapies.
The original study
New Horizons for Precision Medicine in Biliary Tract Cancers.
- Authors
- Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX
- Journal
- Cancer discovery
- Type
- Journal Article, Review
- PMID
- 28818953
Original abstract
Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e.g., radioembolization or external beam radiation), pending confirmation of benefit in randomized studies. Initial trials targeting the epithelial growth factor receptor and angiogenesis pathways have failed to deliver new treatments. Emerging data from next-generation sequencing analyses have identified actionable mutations (e.g., FGFR fusion rearrangements and IDH1 and IDH2 mutations), with several targeted drugs entering clinical development with encouraging results. The role of systemic therapies, including targeted therapies and immunotherapy for BTC, is rapidly evolving and is the subject of this review.Significance: The authors address genetic drivers and molecular biology from a translational perspective, in an intent to offer a clear view of the recent past, present, and future of BTC. The review describes a state-of-the-art update of the current status and future directions of research and therapy in advanced BTC. Cancer Discov; 7(9); 943-62. ©2017 AACR.