Hepatocellular Carcinoma: Molecular Pathogenesis and Therapeutic Advances

SIMPLE SUMMARY: Patients with unresectable hepatocellular carcinoma (HCC), the most common primary tumor of the liver, have poor prognosis and are increasing worldwide. The recent approval of several novel therapies for HCC was long expected, and it will make physician decision-making more challenging. The molecular mechanisms triggered during chronic liver diseases and the cellular cross-talk established with liver cells influence HCC growth and may reduce immune control, making this knowledge relevant to help with clinical decisions. This review analyzes these issues and points to relevant topics for future research. ABSTRACT: 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.