Oncopharmacogenomics of Hepatocellular Carcinoma - A Therapy Related Review

Abstract

Hepatocellular carcinoma (HCC) remains a highly complex disease resistant to commonly used chemotherapy and radiotherapy. As the fifth most common cancer worldwide with the third highest mortality rate and very poorly understood molecular pathways driving hepatocarcinogenesis, new treatment strategies are urgently needed for this devastating disease. The multi kinase inhibitor Sorafenib was the first molecular targeted drug in HCC that led to significant survival benefit in patients with advanced tumors. It is the first drug to be considered standard of care for advanced HCC and supports the importance of molecular therapies in the treatment of this cancer. Analysis of genetic and epigenetic alterations as well as different molecular pathways involved in the development of HCC help to identify potential new druggable targets. A variety of novel compounds are already under preclinical or clinical investigation, and accumulating evidence suggests that combination therapy targeting different pathways will potentiate anti-tumoral effects and will become the future therapeutic approach. In addition, the establishment of a robust molecular classification will pave the way for a more personalized treatment scheme in HCC. In this article a review of the current knowledge of the molecular pathogenesis of HCC and an overview of molecular targeted therapies in the management of HCC are provided.