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What are the key challenges in the pharmacological management of cholangiocarcinoma?

Cholangiocarcinomas are rare cancers that originate from within the biliary tract. There are three main types of cholangiocarcinoma defined by their location within the biliary tract, intrahepatic, perihilar, or distal [1]. These cancers are characterized by low overall survival rates and contribute to ~3% of all cancer-related mortality in the United States. For early stage disease, surgical resection can be curative. However, the tumors may remain asymptomatic until diagnosis at an advanced stage when curative surgery with their removal or with an R0 resection may not be feasible. While locally directed approaches such as photodynamic therapy, radiation, or ablative therapies have been used, their success rates have been modest, and their benefit for advanced disease have been limited. This highlights the dire need for earlier timely diagnosis as well as for an expanded armamentarium of more effective systemic therapies for advanced or metastatic disease. Until recently, pharmacotherapeutic options for systemic therapy were limited to chemotherapy. However, several new therapies targeting specific molecular pathways have now been approved for cholangiocarcinoma. The advent of these and other options dramatically alters the treatment landscape and management approach to these cancers.