Molecular targeted therapy for hepatocellular carcinoma

Abstract

A majority of patients with HCC present with advanced disease and are not candidates for liver transplantation, surgical resection, or regional therapy. Systemic cytotoxic chemotherapy agents are minimally effective, can have significant toxicity, and have not been shown to improve patient survival. Hepatocellular carcinomas are inherently chemotherapy-resistant tumors and are known to overexpress the multidrug resistance genes. Hepatocellular carcinoma is a very heterogeneous disease in terms of its etiology, molecular carcinogenic mechanisms, and biological behavior, which complicate our ability to identify rational molecular therapeutic "targets." Nearly every pathway involved in carcinogenesis is altered to some degree in HCC. Changes in hepatocyte growth factor expression, intracellular signaling, protease and matrix metalloproteinase expression, and oncogene expression are seen in HCC. The recent demonstration, in randomized clinical trials, of survival benefit for HCC patients treated with the oral agent sorafenib is encouraging progress in the development of molecularly targeted anticancer agents in HCC.

Targeting autophagy enhances sorafenib lethality for hepatocellular carcinoma via ER stress-related apoptosis

“…These events are prototypical Recent advances in targeted molecular therapy have shed light on the treatment of advanced HCC. 27 Sorafenib is the only drug which has been demonstrated as effective in a recent randomized, placebo-controlled study (SHARP). 28 However, development of resistance and limited efficacy of sorafenib in advanced HCC patients are deficiencies of the therapy.…”

Anti-Cancer Activity of Brachyuran Crab Dromia dehaani (Rathbun, 1923)

“…Methyl spongoate displays potent toxicity against six hepatocellular carcinoma cell lines, with IC 50 values ranging from 1.7-9 μM. It is known that advanced hepatocellular carcinomas are generally resistant to anticancer drugs because of the multidrug resistant (MDR) phenomena (Thomas, 2009;Papatheodoridis et al, 2010). In the A549 cell lines the IC 50 was 75 μg mLG 1 .…”

Differential Expression of IQGAP1/2 in Hepatocellular Carcinoma and its Relationship with Clinical Outcomes

“…Predisposing factors for HCC include chronic hepatitis B and C virus infections, exposure to aflatoxin B1, chronic alcohol consumption, and any hepatic diseases associated with cirrhosis (Thomas, 2009). The current treatments for HCC with established efficacy include: surgical resection/liver transplantation, transcatherter arterial chemoembolization, percutaneous radiofrequency ablation, percutaneous ethanol injection, percutaneous microwave coagulation therapy and molecular targeted therapy (e.g.…”