Published online Dec 27, 2014. doi: 10.4254/wjh.v6.i12.830
Revised: September 29, 2014
Accepted: October 28, 2014
Published online: December 27, 2014
As the leading cause of disease-related deaths, cancer is a major public health threat worldwide. Surgical resection is still the first-line therapy for patients with early-stage cancers. However, postoperative relapse and metastasis remain the cause of 90% of deaths of patients with solid organ malignancies, including hepatocellular carcinoma (HCC). With the rapid development of molecular biology techniques in recent years, molecularly targeted therapies using monoclonal antibodies, small molecules, and vaccines have become a milestone in cancer therapeutic by significantly improving the survival of cancer patients, and have opened a window of hope for patients with advanced cancer. Hypervascularization is a major characteristic of HCC. It has been reported that anti-angiogenic treatments, which inhibit blood vessel formation, are highly effective for treating HCC. However, the efficacy and safety of anti-angiogenesis therapies remain controversial. Sorafenib is an oral multikinase inhibitor with anti-proliferative and anti-angiogenic effects and is the first molecular target drug approved for the treatment of advanced HCC. While sorafenib has shown promising therapeutic effects, substantial evidence of primary and acquired resistance to sorafenib has been reported. Numerous clinical trials have been conducted to evaluate a large number of molecularly targeted drugs for treating HCC, but most drugs exhibited less efficacy and/or higher toxicity compared to sorafenib. Therefore, understanding the mechanism(s) underlying sorafenib resistance of cancer cells is highlighted for efficiently treating HCC. This concise review aims to provide an overview of anti-angiogenesis therapy in the management of HCC and to discuss the common mechanisms of resistance to anti-angiogenesis therapies.
Core tip: Hepatocellular carcinoma (HCC) is a devastating disease with a high mortality rate. For a long period of time, no effective treatment options are available for patients with advanced HCC. During the last decade, molecularly targeted therapies have been introduced into the treatment of advanced HCC. However, the efficacy and safety of molecularly targeted therapies remain controversial. In addition, primary or acquired drug resistance limits the activity of molecularly targeted agents, but the underlying mechanisms have not been fully understood. This concise review aims to provide an overview of anti-angiogenesis therapy in the treatment of HCC.