Hepatocellular carcinoma: Molecular pathogenesis and therapeutic advances

Hepatocellular carcinoma (HCC), the most common form of liver cancer, continues to be a serious medical problem with poor prognosis, without major therapeutic improvement for years and increasing incidence. Fortunately, advances in systemic treatment options are finally arriving for HCC patients. After a decade of sorafenib as a standard therapy for advanced HCC, several tyrosine kinase inhibitors (TKIs), antiangiogenic antibodies, and immune checkpoint inhibitors have reached the clinic. Although infections by hepatitis B virus and hepatitis C virus remain principal factors for HCC development, the rise of non- alcoholic steatohepatitis from diabetes mellitus or metabolic syndrome is impeding HCC decline. Knowledge of specific molecular mechanisms, based on the etiology and the HCC microenvironment that influence tumor growth and immune control, will be crucial for physician decision-making among a variety of drugs to prescribe. In addition, markers of treatment efficacy are needed to speed the movement of patients towards other potentially effective treatments. Consequently, research to provide scientific data for the evidence-based management of liver cancer is guaranteed in the coming years and discussed here.This research was funded by Instituto de Salud Carlos III, grant number PI19/01410 to M.M.; CIBEREHD and CIBERNED; Ministerio de Ciencia e Innovación, grant numbers RTI2018-095672-B-I00 to A.M. and P.G.F. and RTI2018-095572-B-100 to A.C.; and co-funded by FEDER (Fondo Europeo de Desarrollo Regional, Unión Europea); Ayuda Extraordinaria CSIC 2021AEP095 to A.M. and P.G.F., AGAUR, grant number 2017_SGR_177 to A.M.; Fundació la Marató de TV3 to A.M.; and CERCA Programme/Generalitat de Catalunya