仑伐替尼联合免疫检查点抑制剂治疗恶性肿瘤协同效应的机制研究进展

Progression on the mechanism of synergistic effect in lenvatinib combined with immune checkpoint inhibitors

抗血管生成靶向药物联合免疫检查点抑制剂(ICIs)有望通过协同效应提高ICIs或抗血管生成靶向药物的治疗效果。仑伐替尼是多靶点酪氨酸激酶抑制剂,具有强大的抗血管生成活性,并且能够与PD-1/PD-L1抑制剂发挥协同效应,从而增强PD-1/PD-L1抑制剂的抗肿瘤作用。仑伐替尼联合PD-1抑制剂组合疗法于2021年通过美国食品药品监督管理局(FDA)的批准,用于治疗晚期子宫内膜癌和晚期肾细胞癌患者。基于抗血管生成靶向药物联合ICIs在肿瘤领域展现出的巨大潜力,本文以仑伐替尼联合ICIs为例,着重探讨抗血管生成靶向药物与PD-1/PD-L1抑制剂联合治疗的机制,为更好地运用该类联合治疗策略提供依据。

The combination of anti-angiogenic targeted drugs with immune checkpoint inhibitors(ICIs)is expected to obviously improve the therapeutic effect of ICIs or anti-angiogenic targeted drugs through synergistic effect.Lenvatinib is a multi-target tyrosine kinase inhibitor with strong antiangiogenic activity and synergistic effect with PD-1/PD-L1 inhibitor to enhance the antitumor effect of PD-1/PD-L1 inhibitor.The combination therapy of lenvatinib with a PD-1 inhibitor was approved by the US Food and Drug Administration(FDA)in 2021 for the treatment of patients with advanced endometrial cancer and advanced renal cell cancer.Based on the great potential of anti-angiogenesis targeted drugs combined with ICIs in the tumor field,this paper takes lenvatinib combined with ICIs as an example to focus on the mechanism of anti-angiogenesis targeted drugs combined with PD-1/PD-L1 inhibitors,so as to provide a basis for better application of such combination therapy strategies.