NOTCH1 and cholangiocarcinoma: Furthermore, mutations occurred in relevant genes of several more pathways both in CCA cell lines and tissue samples: the PI3K pathway (e.g., PIK3CA, TSC1 and 2, AKT1, and MTOR), the Notch pathway (NOTCH1-4), which has been proven to be a prerequisite for cholangiocarcinogenesis [40,41], and the cell cycle/ apoptosis regulating pathway (RB1, FBXW7, TP53).