Yang Chen, Zhang Hailin, Zhang Linmeng, Zhu Andrew X, Bernards René, Qin Wenxin, Wang Cun
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Nat Rev Gastroenterol Hepatol. 2023 Apr;20(4):203-222. doi: 10.1038/s41575-022-00704-9. Epub 2022 Nov 11.
Hepatocellular carcinoma (HCC) is one of the most common solid malignancies worldwide. A large proportion of patients with HCC are diagnosed at advanced stages and are only amenable to systemic therapies. We have witnessed the evolution of systemic therapies from single-agent targeted therapy (sorafenib and lenvatinib) to the combination of a checkpoint inhibitor plus targeted therapy (atezolizumab plus bevacizumab therapy). Despite remarkable advances, only a small subset of patients can obtain durable clinical benefit, and therefore substantial therapeutic challenges remain. In the past few years, emerging systemic therapies, including new molecular-targeted monotherapies (for example, donafenib), new immuno-oncology monotherapies (for example, durvalumab) and new combination therapies (for example, durvalumab plus tremelimumab), have shown encouraging results in clinical trials. In addition, many novel therapeutic approaches with the potential to offer improved treatment effects in patients with advanced HCC, such as sequential combination targeted therapy and next-generation adoptive cell therapy, have also been proposed and developed. In this Review, we summarize the latest clinical advances in the treatment of advanced HCC and discuss future perspectives that might inform the development of more effective therapeutics for advanced HCC.
肝细胞癌（HCC）是全球最常见的实体恶性肿瘤之一。很大一部分HCC患者在晚期才被诊断出来，仅适合接受全身治疗。我们见证了全身治疗从单药靶向治疗（索拉非尼和仑伐替尼）发展到检查点抑制剂加靶向治疗的联合治疗（阿替利珠单抗加贝伐珠单抗治疗）。尽管取得了显著进展，但只有一小部分患者能获得持久的临床获益，因此仍存在重大的治疗挑战。在过去几年中，新兴的全身治疗方法，包括新的分子靶向单药治疗（如多纳非尼）、新的免疫肿瘤学单药治疗（如度伐利尤单抗）和新的联合治疗（如度伐利尤单抗加曲美木单抗），在临床试验中显示出了令人鼓舞的结果。此外，许多有可能改善晚期HCC患者治疗效果的新型治疗方法，如序贯联合靶向治疗和下一代过继性细胞治疗，也已被提出并开发。在本综述中，我们总结了晚期HCC治疗的最新临床进展，并讨论了可能为开发更有效的晚期HCC治疗方法提供参考的未来前景。
