Cholangiocarcinoma: Disease pathogenesis and new treatment paradigms

Cholangiocarcinoma (CCA) is a malignancy arising in the biliary tree. Its incidence rates have increased, and it has surpassed gallbladder carcinoma as the most common biliary tract malignancy. Most patients are diagnosed with advanced stage disease and are not amenable to potentially curative surgical therapies. The prognosis is dismal with a median survival of <24 months. Novel possible epidemiologic risk factors (i.e., diabetes, cirrhosis, metabolic syndrome) have been identified. Based upon clinical behavior and distinct molecular patterns, intrahepatic, perihilar, and distal CCAs are characterized as distinct malignancies that need to be treated as such in their management and clinical trials. While cholestasis and inflammation are key factors for all three CCA subtypes, their genetic profile differs. Because knowledge of the genetic landscape of CCA has resulted in multiple new therapeutic strategies and clinical trials, it will become increasingly possible to develop precision medicine-based therapies for CCA patients.