Department of Pathology, The University of Hong Kong, Hong Kong.
State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong.
Hepatology. 2021 Oct;74(4):2264-2276. doi: 10.1002/hep.31840. Epub 2021 Jun 21.
Hepatocellular carcinoma (HCC) is one of the deadliest cancers because of late symptom manifestation leading to delayed diagnosis, which limits patients with HCC in terms of receiving curative surgical treatment. There are only a few therapeutic options for patients with advanced HCC. The emergence of immune checkpoint inhibitors (ICIs) brings HCC treatment to a stage at which nivolumab, an anti-programmed cell death protein 1 monoclonal antibody, achieves a 20% response rate. However, the large proportion of unresponsive patients drives the exploration of therapeutic strategies to improve ICIs' efficacy. Recent preclinical and clinical studies have suggested that ICIs, when used in combinations or when used with other cancer therapies, might elicit synergistic antitumor effects. However, the mechanistic rationales guiding different drug combinations to maximize this synergy remain largely ambiguous. In this review, we discuss different drug combinations used in HCC and the underlying mechanistic rationales, aiming to enhance the understanding of how these treatments can achieve synergy. This knowledge sets the foundation for the development of more effective and promising combination therapies for HCC.
肝细胞癌（HCC）是最致命的癌症之一，因为其症状表现较晚，导致诊断延迟，这限制了 HCC 患者接受根治性手术治疗的机会。晚期 HCC 患者仅有少数治疗选择。免疫检查点抑制剂（ICIs）的出现将 HCC 治疗带到了一个新阶段，其中抗程序性细胞死亡蛋白 1 单克隆抗体纳武利尤单抗的反应率达到 20%。然而，大量无反应的患者促使人们探索改善 ICI 疗效的治疗策略。最近的临床前和临床研究表明，ICI 联合使用或与其他癌症疗法联合使用可能会产生协同的抗肿瘤作用。然而，指导不同药物组合以最大化这种协同作用的机制合理性在很大程度上仍不清楚。在这篇综述中，我们讨论了 HCC 中使用的不同药物组合及其潜在的机制合理性，旨在增强对这些治疗方法如何实现协同作用的理解。这些知识为开发更有效和更有前途的 HCC 联合治疗方法奠定了基础。
