Molecular Alterations and Pathways in Intrahepatic Cholangiocarcinoma: Available Evidence and New Perspectives

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer arising within the liver from the bile ducts, and it is characterized by limited therapeutic options and a poor prognosis. This neoplasm exhibits both high intra-tumor and inter-tumor heterogeneity and many oncogenic and tumor suppressor genes are involved in its development and progression. Here, we summarize the major pathways and driver genes involved in the genesis and progression of iCCA, with a special look at their potential therapeutic values. We approach not only the well-known FGFR, IDH and HER2 alterations but also delve into less known cellular pathways such as cell surface receptors, cellular signaling pathways, tumor suppressor genes and metabolic pathways. The aim of our review is therefore not only to summarize the available evidence on singular pathways/alterations but also to foster and promote new investigations into lesser known alterations that could be present in each singular iCCA case.