School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (Usern), Tehran, Iran.
Expert Rev Anticancer Ther. 2021 Dec;21(12):1355-1370. doi: 10.1080/14737140.2021.1996230. Epub 2021 Nov 8.
Lung cancer is known for its high mortality rate and prevalence in the world today. For decades, chemotherapy has been used as the main treatment for this cancer, but this has changed over time. Immune checkpoint inhibitors (ICIs) such as programmed death 1 and programmed death-ligand 1 (PD-1/PD-L1) blocking agents have been assessed in numerous clinical trials as single or combination therapy and have shown overall promising results. Nevertheless, various challenges have been encountered, which cast doubts over this method.
We provide an introduction to the mechanisms underlying the PD-1/PD-L1 pathway. Then, we discuss the latest results from the most leading-edge studies evaluating PD-1/PD-L1 inhibitors in different lines of lung cancer therapy (some of which have gained FDA approval), potential biomarkers, and major challenges of ICI therapy.
Currently, the standard of care (SoC) for lung cancer consists mostly of chemotherapeutics. With further studies and ongoing trials evaluating novel ICI therapy, FDA has been approving specific ICI therapeutics, including PD-1/PD-L1 inhibitors, for particular types of lung cancer. However, for ICIs to play a key role in SoC, we need to overcome the major challenges of ICI therapy.
肺癌是当今世界死亡率和发病率较高的疾病。几十年来,化疗一直是治疗这种癌症的主要方法,但随着时间的推移,这种情况发生了变化。程序性死亡受体 1(PD-1)和程序性死亡配体 1(PD-L1)阻断剂等免疫检查点抑制剂(ICI)已在众多临床试验中作为单一或联合疗法进行评估,总体结果令人鼓舞。然而,已经遇到了各种挑战,这使得人们对这种方法产生了怀疑。
我们介绍了 PD-1/PD-L1 通路的作用机制。然后,我们讨论了评估 PD-1/PD-L1 抑制剂在不同肺癌治疗线中的最新研究结果(其中一些已获得 FDA 批准)、潜在的生物标志物和 ICI 治疗的主要挑战。
目前,肺癌的标准治疗(SoC)主要包括化疗药物。随着进一步的研究和正在进行的临床试验评估新型 ICI 治疗,FDA 已批准特定的 ICI 治疗药物,包括 PD-1/PD-L1 抑制剂,用于特定类型的肺癌。然而,为了使 ICIs 在 SoC 中发挥关键作用,我们需要克服 ICI 治疗的主要挑战。