免疫检查点抑制剂在非小细胞肺癌中的应用:鸟瞰全局。

Immune checkpoint inhibitors in non-small cell lung cancer: A bird's eye view.

机构信息

Institute of Pharmacy, Nirma University, Ahmedabad, India.

Institute of Pharmacy, Nirma University, Ahmedabad, India.

出版信息

Life Sci. 2019 Sep 15;233:116713. doi: 10.1016/j.lfs.2019.116713. Epub 2019 Aug 3.

Abstract

Lung cancer is the leading cause of cancer-related mortality worldwide. Treatment with immunotherapy has made a significant impact on the outcomes for those patients suffering from lung cancer and its usage is currently an established treatment modality. Immune checkpoint inhibition that has blocking antibodies which target cytotoxic T-lymphocyte antigen-4 (CTLA-4) along with the programmed cell death protein 1 (PD-1) pathway [programmed death - 1/programmed death-ligand 1 (PD-L1)] have shown promising results for numerous malignancies. Nivolumab and pembrolizumab have been approved as PD-1 blocking antibodies while atezolizumab, avelumab, and durvalumab are approved as PD-L1 blocking antibodies by 'US Food and Drug Administration'. Immune checkpoint inhibitors have been found to statistically improve the survival of patients with lung cancer and have emerged as the primary immunotherapy in lung cancer and have changed the treatment paradigm for advanced disease. Despite such benefits, treatment with immune checkpoint inhibitors is associated with a unique pattern of immune-related adverse effects or side effects. Also, resistance is routinely developing in patients treated with immune checkpoint inhibitors. The current review provides an overview of immune checkpoint inhibitor treatment in lung cancer, its resistance, and adverse effects.

摘要

肺癌是全球癌症相关死亡的主要原因。免疫疗法的治疗对肺癌患者的治疗结果产生了重大影响,目前已成为一种既定的治疗方式。免疫检查点抑制作用具有阻断抗体,针对细胞毒性 T 淋巴细胞抗原-4(CTLA-4)以及程序性细胞死亡蛋白 1(PD-1)途径[程序性死亡-1/程序性死亡配体 1(PD-L1)],已显示出对多种恶性肿瘤的良好效果。纳武单抗和派姆单抗已被批准为 PD-1 阻断抗体,而阿特珠单抗、avelumab 和度伐鲁单抗则被美国食品和药物管理局(FDA)批准为 PD-L1 阻断抗体。免疫检查点抑制剂已被发现可从统计学上改善肺癌患者的生存率,已成为肺癌的主要免疫疗法,并改变了晚期疾病的治疗模式。尽管有这些益处,但免疫检查点抑制剂的治疗与独特的免疫相关不良事件或副作用有关。此外,接受免疫检查点抑制剂治疗的患者通常会产生耐药性。本综述提供了肺癌中免疫检查点抑制剂治疗、耐药性和不良反应的概述。

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