为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Evolving therapeutic landscape of advanced hepatocellular carcinoma.
Evolving therapeutic landscape of advanced hepatocellular carcinoma.
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肝细胞癌(HCC)是全球最常见的实体恶性肿瘤之一。大部分HCC患者确诊时已处于晚期,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)到检查点抑制剂联合靶向治疗(阿替利珠单抗联合贝伐珠单抗治疗)的演变。尽管取得了显著进展,但只有一小部分患者能够获得持久的临床获益,因此仍存在巨大的治疗挑战。在过去几年中,新兴的全身治疗,包括新的分子靶向单药治疗(例如多纳非尼)、新的免疫肿瘤单药治疗(例如度伐利尤单抗)和新的联合治疗(例如度伐利尤单抗联合替西木单抗),在临床试验中显示出令人鼓舞的结果。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,并讨论了可能为晚期HCC更有效治疗方法的开发提供信息的未来展望。
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.
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