Chuma Makoto, Terashita Katsumi, Sakamoto Naoya
Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo.
Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.
Hepatol Res. 2015 Oct;45(10):E1-E11. doi: 10.1111/hepr.12459. Epub 2015 Jan 9.
Hepatocellular carcinoma (HCC) can be lethal due to its aggressive course and lack of effective systemic therapies for advanced disease. Sorafenib is the only systemic therapy that has demonstrated an overall survival benefit in patients with advanced HCC, and new agents for treatment of advanced HCC are needed. The multiple pathways involved in HCC oncogenesis, proliferation and survival provide many opportunities for the development of molecularly targeted therapies. Molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for treatment of advanced HCC. Agents targeting vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-mesenchymal-epithelial transition factor-1 and mammalian target of rapamycin signaling have been actively explored. This article focuses on the evaluation of molecular agents targeting pathogenic HCC and provides a review of recently completed phase III drug studies (e.g. involving sorafenib, sunitinib, brivanib, linifanib, erlotinib, everolimus, ramucirumab or orantinib) and ongoing drug studies (e.g. involving lenvatinib, regorafenib, tivantinib or cabozantinib) of molecularly targeted agents in advanced HCC, including a brief description of the biologic rationale behind these agents.
肝细胞癌（HCC）因其侵袭性病程以及缺乏针对晚期疾病的有效全身治疗方法而可能致命。索拉非尼是唯一一种已证明能使晚期HCC患者总生存期受益的全身治疗药物，因此需要用于治疗晚期HCC的新药物。HCC发生、增殖和存活过程中涉及的多种途径为分子靶向治疗的发展提供了诸多机会。治疗晚期HCC的感兴趣分子靶点已从血管生成扩展至癌细胞导向的致癌信号通路。针对血管内皮生长因子受体、表皮生长因子受体、成纤维细胞生长因子受体、血小板衍生生长因子受体、c-间充质-上皮转化因子-1和雷帕霉素哺乳动物靶点信号传导的药物已得到积极探索。本文重点评估针对致病性HCC的分子药物，并综述最近完成的III期药物研究（如涉及索拉非尼、舒尼替尼、布立尼布、利尼伐尼、厄洛替尼、依维莫司、雷莫西尤单抗或奥拉替尼）以及正在进行的晚期HCC分子靶向药物研究（如涉及乐伐替尼、瑞戈非尼、替凡替尼或卡博替尼），包括对这些药物背后生物学原理的简要描述。
