Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy

Abstract

Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called "driver mutations". The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy. In this review, we summarized currently discovered driver mutations and corresponding signaling pathways, made an overview of identification methods of driver mutations and genes, and classified targeted drugs for HCC. The knowledge of mutational landscape deepen our understanding of carcinogenesis and promise future precision medicine for HCC patients.

Keywords: driver identification; driver mutations; hepatocellular carcinoma; precision medicine; targeted therapy.

Figure 1. Targeted therapies for HCC and their target signaling pathways

Drugs in orange boxes (sorafenib and regorafenib) have been approved by FDA for the treatment of patients in HCC, while others are being evaluated in Phase II or III clinic trials.