Mechanistic insights into liver-fluke-induced bile-duct cancer

Liver fluke infection is a major risk for cholangiocarcinoma (CCA). It has been established that the Asian liver flukes, Clonorchis sinensis and Opisthorchis viverrini secrete growth factors, digestive enzymes, and extracellular vesicles (EVs) which contribute to abnormal cell development in the bile ducts where the worms reside. These secretions - combined with aberrant inflammation and repeated cycles of chronic wounding at the site of parasite attachment and grazing on the epithelium - promote biliary hyperplasia and fibrosis and ultimately malignant transformation. Application of post-genomic and gene-editing tools to the study of liver fluke immunobiology and pathogenesis has accelerated the discovery of essential virulence factors to which targeted therapies and diagnostics can be directed.