Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Ann Surg Oncol. 2010 May;17(5):1247-56. doi: 10.1245/s10434-010-0975-6. Epub 2010 Apr 20.
Despite decades of efforts by many investigators, systemic chemotherapy or hormone therapy have failed to demonstrate improved survival in patients with advanced hepatocellular carcinoma (HCC). On the basis of placebo-controlled, randomized phase III trials, sorafenib has shown improved survival benefits in advanced HCC and has set a new standard for future clinical trials. The successful clinical development of sorafenib in HCC has ushered in the era of molecularly targeted agents in this disease, which is discussed in this educational review.
Ongoing studies are evaluating the efficacy and tolerability of combining sorafenib with erlotinib and other targeted agents or chemotherapy. Many molecularly targeted agents that inhibit angiogenesis, epidermal growth factor receptor, and mammalian target of rapamycin are at different stages of clinical development in advanced HCC. Combining targeted agents that inhibit different pathways in hepatocarcinogenesis is an area of active investigation. Future research should continue to unravel the mechanism of hepatocarcinogenesis and to identify key relevant molecular targets for therapeutic intervention. Identification and validation of potential surrogate and predictive biomarkers holds promise to individualize patients' treatment to maximize clinical benefit and minimize the toxicity and cost of targeted agents. We hope that we will continue to improve the efficacy of systemic therapy in advanced HCC in the coming years.
尽管许多研究人员经过几十年的努力，系统化疗或激素治疗未能显示在晚期肝细胞癌（HCC）患者中改善生存。基于安慰剂对照、随机 III 期试验，索拉非尼在晚期 HCC 中显示出改善的生存获益，并为未来的临床试验设定了新标准。索拉非尼在 HCC 中的成功临床开发开创了该疾病中分子靶向药物的时代，这在本教育综述中进行了讨论。
正在进行的研究评估了索拉非尼与厄洛替尼和其他靶向药物或化疗联合使用的疗效和耐受性。许多抑制血管生成、表皮生长因子受体和哺乳动物雷帕霉素靶蛋白的分子靶向药物在晚期 HCC 的不同临床开发阶段。联合抑制肝癌发生中不同途径的靶向药物是一个积极研究的领域。未来的研究应继续阐明肝癌发生的机制，并确定用于治疗干预的关键相关分子靶点。潜在的替代和预测性生物标志物的鉴定和验证有望使患者的治疗个体化，以最大限度地提高临床获益并最小化靶向药物的毒性和成本。我们希望在未来几年中继续提高晚期 HCC 系统治疗的疗效。
