Abstract
Precision medicine has become a dominant theme in the treatment of biliary tract cancers (BTCs). Although prognosis remains poor, technologies for improved molecular characterization along with the US Food and Drug Administration approval of several targeted therapies have changed the therapeutic landscape of advanced BTC. The hallmark of BTC oncogenesis is chronic inflammation of the liver and biliary tract regardless of the anatomical subtype. Subtypes of BTC correspond to distinct molecular characteristics, making BTC a molecularly heterogenous collection of tumors. Collectively, up to 40% of BTCs harbor a potentially targetable molecular abnormality, and the National Comprehensive Cancer Network guidelines recommend molecular profiling for all patients with advanced BTC. Use of circulating tumor DNA, immunohistochemistry, and next-generation sequencing continues to expand the utility for biomarker-driven management and molecular monitoring of BTC. Improving outcomes using biomarker-agnostic treatment for nontargetable tumors also remains a priority, and combinational treatment strategies such as immune checkpoint inhibition plus chemotherapy hold promise for this subgroup of patients.
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