Molecular mechanisms of tumor initiation in biliary tract cancers

Biliary tract cancers including cholangiocarcinomas and gallbladder cancers are aggressive malignancies. Earlier diagnosis and treatment of these tumors are required to improve prognosis. In the present work, we aimed to better understand the molecular mechanisms of tumor initiation in biliary tract cancers using mouse models of tumorigenesis and spatial transcriptomic analyses of human samples. We found precursor lesions of intrahepatic cholangiocarcinoma in a mouse model recapitulating faithfully human pathology and we showed that Tensin-4 promotes tumor progression. We tried to generate a new mouse model of gallbladder cancer to study specifically this entity. Unfortunately, several attempts gave negative results. Finally, a spatial transcriptomic analysis of human gallbladder cancer and precursor lesions showed patient-specific modes of tumor progression that could be driven by a repression of Semaphorin 4A.