Division of Hematology/Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095, USA.
Semin Liver Dis. 2013 Feb;33 Suppl 1:S11-9. doi: 10.1055/s-0033-1333632. Epub 2013 Mar 1.
Treatment of advanced-stage hepatocellular carcinoma (HCC) remains a challenge because of the complex nature of the disease and the lack of available therapies. The antiangiogenic multikinase inhibitor sorafenib is the first therapy to demonstrate a significant overall survival benefit in advanced HCC. However, new agents for both first- and second-line 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. Many novel agents are under investigation in phase III trials in advanced HCC, including antiangiogenic multikinase inhibitors (e.g., brivanib, sunitinib, linifanib) and inhibitors of the mammalian target of rapamycin (mTOR) pathway (e.g., everolimus). Although these therapies have demonstrated some utility as single agents in advanced HCC, rational combinations of therapies are likely to provide greater success. Current research efforts are directed at combining agents targeting different molecular pathways (e.g., sorafenib in combination with erlotinib) and combining molecularly targeted agents with systemic chemotherapy or transarterial chemoembolization (TACE). Therapies targeting other molecular pathways in HCC are in early development; future research will focus on discovering additional targets for therapy and identifying biomarkers that predict the success of current therapies.
治疗晚期肝细胞癌（HCC）仍然是一个挑战，因为该疾病的性质复杂，且缺乏可用的治疗方法。抗血管生成多激酶抑制剂索拉非尼是首个在晚期 HCC 中显示出总生存期显著改善的治疗药物。然而，仍需要新的药物用于晚期 HCC 的一线和二线治疗。HCC 发生、增殖和存活所涉及的多个途径为分子靶向治疗的发展提供了许多机会。许多新型药物正在晚期 HCC 的 III 期临床试验中进行研究，包括抗血管生成多激酶抑制剂（如 brivanib、sunitinib、linifanib）和哺乳动物雷帕霉素靶蛋白（mTOR）通路抑制剂（如依维莫司）。尽管这些疗法作为单一药物在晚期 HCC 中已显示出一定的疗效，但合理的联合治疗可能会取得更大的成功。目前的研究工作旨在将靶向不同分子途径的药物联合使用（例如，索拉非尼联合厄洛替尼），并将分子靶向药物与全身化疗或经动脉化疗栓塞（TACE）联合使用。针对 HCC 中其他分子途径的治疗方法尚处于早期开发阶段；未来的研究将侧重于发现更多的治疗靶点，并确定预测现有治疗方法疗效的生物标志物。
