National Cancer Centre of Singapore, Humphrey Oei Institute of Cancer Research, Division of Cellular and Molecular Research, Laboratory of Molecular Endocrinology, 11 Hospital Drive, 169610, Singapore.
Expert Opin Emerg Drugs. 2010 Mar;15(1):13-26. doi: 10.1517/14728210903571659.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Although patients with early-stage disease have a good prognosis, there has been no effective therapy available for those with advanced disease. Despite the death risk of patients with advanced HCC being reduced with sorafenib therapy, many patients eventually turn out to be refractory to this therapy. Thus, treatment of HCC remains an urgent health concern.
Recent improvement in understanding the pathophysiology of HCC at the molecular level has fostered the development of molecular targeted therapies that specifically block the disrupted pathways.
This review summarizes the preclinical and clinical data from 2004 to 2009 on the efficacy and safety of the emerging drug for the treatment of HCC, including small molecule inhibitors (erlotinib, sunitinib, sorafenib, vandetanib, cediranib, brivanib and dovitinib) and the rationale for combination therapies for patients with advanced HCC.
Understanding the mechanisms of action, safety and efficacy of these new agents and new methods of combining these drugs may help prolong overall survival of patients with HCC and reduce disease recurrence after surgery or ablative therapies.
肝细胞癌(HCC)是全球癌症相关死亡的第三大常见原因。尽管早期疾病患者的预后良好,但对于晚期疾病患者,尚无有效的治疗方法。尽管索拉非尼治疗可降低晚期 HCC 患者的死亡风险,但许多患者最终对此种治疗产生耐药性。因此,HCC 的治疗仍然是一个紧迫的健康问题。
近年来,对 HCC 分子水平病理生理学的认识不断提高,促进了分子靶向治疗的发展,这些治疗方法专门阻断失调的通路。
本文总结了 2004 年至 2009 年期间新兴 HCC 治疗药物的临床前和临床数据,包括小分子抑制剂(厄洛替尼、舒尼替尼、索拉非尼、凡德他尼、西地尼布、brivanib 和多韦替尼)以及联合治疗晚期 HCC 患者的原理。
了解这些新药物的作用机制、安全性和疗效,以及联合使用这些药物的新方法,可能有助于延长 HCC 患者的总生存期,并减少手术后或消融治疗后的疾病复发。