Biliary cancer: intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma vs. gallbladder cancers: classification and therapeutic implications

Biliary cancers (BCs) are rare but heterogeneous, and comprised of intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancers. They may arise along any portion of the bile duct system, from the neoplastic proliferation of cholangiocytes, the epithelium of the bile ducts. While all three anatomic groups fall under BC, our increased understanding has allowed us to rationalize that each may be in fact distinct diseases, with differences in patterns of recurrence and prognosis (1). Pre-clinical studies have reinforced this thought process, where immunohistochemical studies from BC samples revealed phenotypic traits of cholangiocytes and progenitor cells consistent with their anatomic sites of origin, confirming the heterogeneity between the three groups (2). Progenitor cells from the canals of Hering have been identified in IHCC, while those within the peribiliary glands have been identified in EHCC and gallbladder cancers, respectively (2-5). Furthermore, the increased availability of next-generation sequencing panels has facilitated this thought process by allowing us to understand the tumor somatic variants and genomic heterogeneity between the three groups. Herein, we will the current treatment in BC, genomic landscape in BC and its role in treatment selection and integration in clinical trials