是或否:携带有各种驱动基因突变的非小细胞肺癌的免疫治疗困境。
To be, or not to be: the dilemma of immunotherapy for non-small cell lung cancer harboring various driver mutations.
机构信息
Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Baiziting 42, Nanjing, 210009, People's Republic of China.
Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, 210009, People's Republic of China.
出版信息
J Cancer Res Clin Oncol. 2023 Sep;149(12):10027-10040. doi: 10.1007/s00432-023-04919-4. Epub 2023 Jun 1.
INTRODUCTION
Lung cancer is one of primary cancer type with high incidence and mortality, non-small cell lung cancer (NSCLC) is the most common type of lung cncer. For advanced lung cancer, traditional chemotherapy and targeted therapy become difficult to solve the dilemma of further progress. In recent years, with the clinical application of immunotherapy, the therapeutic strategy of lung cancer has changed dramatically. At present, immunotherapy has shown conspicuous efficacy in NSCLC patients with high expression of programmed death-ligand 1 (PD-L1) and high tumor mutational burden (TMB). The discovery of driver mutations brings delightful hope for targeted cancer therapy. However, it remains controversial whether immunotherapy can be used in NSCLC patients with these specific driver mutations.
METHOD
This article summarized the latest research progresses of immunotherapy in advanced NSCLC. We paid close attention to the relevance of various driver mutations and immunotherapy in NSCLC patients, and summarized the predictive effects of several driver mutations and immunotherapy.
RESULTS
The mutations of KRAS, KRAS+TP53, EPHA (especially EPHA5), ZFHX3, ZFHX3+TP53, NOTCH, BRAF and LRP1B+FAT3 have potential to be used as biomarkers to predict the positive effectiveness of immunotherapy. ZFHX3, ZFHX3+TP53, STKII/LKB1+KEAP1+SMARCA4+PBRM1 mutations in LUAD patients get more positive effect in immunotherapy. While the mutations of EGFR, KEAP1, STKII/LKB1+KRAS, EML4-ALK, MET exon 14 skipping mutation, PBRM1, STKII/LKB1+KEAP1+SMARCA4+PBRM1, ERBB2, PIK3CA and RET often indicate poor benefit from immunotherapy.
CONCLUSION
Many gene mutations have been shown to be associated with immunotherapy efficacy. Gene mutations should be combined with PD-L1, TMB, etc. to predict the effect of immunotherapy.
简介
肺癌是发病率和死亡率较高的原发性癌症之一,非小细胞肺癌(NSCLC)是最常见的肺癌类型。对于晚期肺癌,传统化疗和靶向治疗难以解决进一步进展的困境。近年来,随着免疫疗法的临床应用,肺癌的治疗策略发生了巨大变化。目前,免疫疗法在高表达程序性死亡配体 1(PD-L1)和高肿瘤突变负担(TMB)的 NSCLC 患者中显示出显著疗效。驱动基因突变的发现为靶向癌症治疗带来了令人欣喜的希望。然而,免疫疗法是否可用于具有这些特定驱动基因突变的 NSCLC 患者仍存在争议。
方法
本文总结了晚期 NSCLC 免疫治疗的最新研究进展。我们密切关注了各种驱动基因突变与 NSCLC 患者免疫治疗的相关性,并总结了几种驱动基因突变与免疫治疗的预测效果。
结果
KRAS、KRAS+TP53、EPHA(尤其是 EPHA5)、ZFHX3、ZFHX3+TP53、NOTCH、BRAF 和 LRP1B+FAT3 的突变可能成为预测免疫治疗阳性效果的生物标志物。ZFHX3、ZFHX3+TP53、STKII/LKB1+KEAP1+SMARCA4+PBRM1 突变的 LUAD 患者在免疫治疗中获得了更积极的效果。而 EGFR、KEAP1、STKII/LKB1+KRAS、EML4-ALK、MET 外显子 14 跳跃突变、PBRM1、STKII/LKB1+KEAP1+SMARCA4+PBRM1、ERBB2、PIK3CA 和 RET 的突变通常表明免疫治疗获益不佳。
结论
许多基因突变已被证明与免疫治疗疗效相关。基因突变应与 PD-L1、TMB 等结合预测免疫治疗效果。
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