Development of Molecularly Targeted Therapies in Hepatocellular Carcinoma: Where Do We Go Now?

Abstract

Hepatocellular carcinoma (HCC), once considered an orphan disease in the West, has become a global health concern. It is the third leading cause of cancer death worldwide, and its incidence continues to increase. Historically, the development of new systemic agents for advanced HCC has been lacking despite no clear benefit with traditional cytotoxic therapies. Although two randomized studies with sorafenib for the treatment of HCC patients have recently been completed, survival benefits have been modest and highlight the unmet medical need among patients with HCC. Given the clear need, clinical development of novel systemic agents in HCC has begun in earnest. These clinical studies are founded on a growing body of basic and translational science that has identified several potential molecular targets in HCC. The successful development of such targeted agents in the future will be linked to our ability to appropriately select patients for treatment based on their clinical stage (including extent of liver disease and extent of tumor) and on potential predictive markers of response. Here, we review these data in the context of rational drug development in HCC in the front-line setting and in previously treated patients.Clin Cancer Res; 16(2); 390-7.

Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

“…Only 15% are eligible for curative treatment [1] . The 2 year recurrence rate can reach up to 50%, even for patients undergoing surgery, with a 10 year rate of 76% [2] .…”

Phase II, Open-Label Study of Brivanib as Second-Line Therapy in Patients with Advanced Hepatocellular Carcinoma

“…With regard to HCC, the only systemic agent that has been shown to improve survival is sorafenib, an oral multikinase inhibitor (5,6). Beyond sorafenib, several studies are evaluating novel combinations (9), and although benefits have been observed with sorafenib, other single agents (e.g., sunitinib) have not shown efficacy in HCC (10).…”

Introductory Chapter: Updates on the Management of Hepatocellular Carcinoma

“…Only 15-30% of patients present in early stage HCC and can receive curative treatments [4]. This is mainly due to liver cirrhosis associated with hepatocarcinoma, and the late presentation reported in most patients.…”