PIK3CA and cholangiocarcinoma: Consequently, a number of important signaling pathways involved in CCA have been discovered including RAF/mitogen-activated protein kinase (MEK)/MAPK, transforming growth factor-β (TGF-β)/SMADs, phosphatidylinositol 3-kinase (PI3K)/AKT, WNT, interleukin-6 (IL-6)/STAT-3, and NOTCH [18,19].