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Indexed/Abstracted in: CAB, EMBASE, PubMed/MEDLINE, Scopus, Emerging Sources Citation Index
Online ISSN 1827-1642
Emmet JORDAN 1, Maria Ignez F. BRAGHIROLI 1, Maeve A. LOWERY 1, 2
1 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2 Department of Medicine, Weill Cornell Medical College, New York, NY, USA
Biliary tract cancers (BTC) are a rare, heterogenous group encompassing gallbladder cancers and cholangiocarcinomas that are most commonly diagnosed in the locally advanced or metastatic setting. While systemic chemotherapy provides modest clinical benefit, there is a clear need for the development of more effective treatment strategies. Advances in next generation sequencing assays have underscored the molecular heterogeneity within BTC and identified the potential to exploit potential vulnerabilities in signaling pathways offering a personalized approach to treatment. In this article we review key genetic alterations detected in BTC and provide an overview of prior, current and the emerging role of molecular therapeutics in BTC. We also discuss the evaluation of immunotherapy in completed and ongoing trials as a potential treatment modality in BTC. Overall, prior studies using targeted agents were undermined by assessment of such agents within an unselected patient population. In contrast current and planned novel treatment approaches in BTC are now more frequently using molecular profiling to select patients for a molecularly targeted approach or incorporating biomarkers to inform studies in unselected patients. Currently, no approved molecular therapy for BTC exists, however by incorporating molecular profiling in directing novel targeted therapy trial enrollment and assessment along with the ongoing appraisal of immunotherapy we anticipate significant incremental progress over the coming decade.