Sun Hong, Zhu Man-Sheng, Wu Wen-Rui, Shi Xiang-De, Xu Lei-Bo
Hong Sun, Department of Transplant Medicine, University Hospital Münster, 48149 Münster, Germany.
World J Hepatol. 2014 Dec 27;6(12):830-5. doi: 10.4254/wjh.v6.i12.830.
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.
作为疾病相关死亡的主要原因，癌症是全球重大的公共卫生威胁。手术切除仍是早期癌症患者的一线治疗方法。然而，术后复发和转移仍是包括肝细胞癌（HCC）在内的实体器官恶性肿瘤患者90%死亡的原因。近年来，随着分子生物学技术的快速发展，使用单克隆抗体、小分子和疫苗的分子靶向治疗通过显著提高癌症患者的生存率，成为癌症治疗的一个里程碑，并为晚期癌症患者打开了一扇希望之窗。血管过度生成是HCC的一个主要特征。据报道，抑制血管形成的抗血管生成治疗对治疗HCC非常有效。然而，抗血管生成治疗的疗效和安全性仍存在争议。索拉非尼是一种具有抗增殖和抗血管生成作用的口服多激酶抑制剂，是首个被批准用于治疗晚期HCC的分子靶向药物。虽然索拉非尼已显示出有前景的治疗效果，但已有大量关于对索拉非尼原发性和获得性耐药的报道。已经进行了大量临床试验来评估大量用于治疗HCC的分子靶向药物，但与索拉非尼相比，大多数药物疗效较低和/或毒性较高。因此，了解癌细胞对索拉非尼耐药的机制对于有效治疗HCC至关重要。本简要综述旨在概述抗血管生成治疗在HCC管理中的应用，并讨论抗血管生成治疗耐药的常见机制。
