Molecular Pathogenesis of Cholangiocarcinoma

It has become increasingly apparent of late that inflammation plays an integral role in a spectrum of malignancies including cholangiocarcinoma (CCA). Primary sclerosing cholangitis with chronic inflammation is the most common risk factor for CCA in the Western world. Recent work has highlighted that inflammatory pathways are essential in carcinogenesis and tissue invasion and migration. Inflammation advances carcinogenesis by induction of DNA damage, evasion of apoptosis, promotion of cell proliferation, and neoangiogenesis. CCA is characterized by the presence of a desmoplastic stroma consisting of cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating lymphocytes. This rich inflammatory milieu is vital to the cancer ecosystem, and targeting its components represents an attractive therapeutic option.