Abstract:
Kirsten rat sarcoma viral oncogene homologue (KRAS) gene mutations are among the most commonly found oncogenic alterations in non-small cell lung cancer (NSCLC) patients. Unfortunately, KRAS mutations have been considered \"undruggable\" for many years, making treatment options very limited. Immunotherapy targeting programmed death-ligand 1 (PD-L1), programmed death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) has emerged as a promising therapeutic option for NSCLC patients. However, some studies have suggested a lower response rate to immunotherapy in KRAS-mutated NSCLC patients with the coexistence of mutations in the STK11 (Serine/Threonine Kinase 11) gene. However, recent clinical trials have shown promising results with the combination of immunotherapy and chemotherapy or immunotherapy and KRAS inhibitors (sotorasib, adagrasib) in such patients. In other studies, the high efficacy of immunotherapy has been demonstrated in NSCLC patients with mutations in the KRAS gene that do not coexist with other mutations or coexist with the TP53 gene mutations. In this paper, we review the available literature on the efficacy of immunotherapy in KRAS-mutated NSCLC patients. In addition, we presented single-site experience on the efficacy of immunotherapy in NSCLC patients with KRAS mutations. The effectiveness of chemoimmunotherapy or immunotherapy as well as KRAS inhibitors extends the overall survival of advanced NSCLC patients with the G12C mutation in the KRAS gene to 2-3 years. This type of management has become the new standard in the treatment of NSCLC patients. Further studies are needed to clarify the potential benefits of immunotherapy in KRAS-mutated NSCLC patients and to identify potential biomarkers that may help predict response to therapy.
摘要:
Kirsten大鼠肉瘤病毒癌基因同源(KRAS)基因突变是非小细胞肺癌(NSCLC)患者中最常见的致癌改变。不幸的是,KRAS突变多年来一直被认为是“不可用的”,使治疗选择非常有限。靶向程序性死亡-配体1(PD-L1)的免疫治疗,程序性死亡1(PD-1)和细胞毒性T淋巴细胞抗原4(CTLA-4)已成为NSCLC患者有希望的治疗选择.然而,一些研究表明,在同时存在STK11(丝氨酸/苏氨酸激酶11)基因突变的KRAS突变的NSCLC患者中,免疫治疗的应答率较低.然而,最近的临床试验显示了免疫疗法和化疗或免疫疗法和KRAS抑制剂(sotorasib,adagrasib)在这样的患者中。在其他研究中,在KRAS基因突变不与其他突变共存或与TP53基因突变共存的NSCLC患者中,已经证明了免疫治疗的高疗效.在本文中,我们回顾了关于KRAS突变NSCLC患者免疫治疗疗效的现有文献.此外,我们介绍了KRAS突变NSCLC患者免疫治疗疗效的单中心经验.化学免疫疗法或免疫疗法以及KRAS抑制剂的有效性将具有KRAS基因中G12C突变的晚期NSCLC患者的总生存期延长至2-3年。这种管理方式已成为NSCLC患者治疗的新标准。需要进一步的研究来阐明免疫疗法在KRAS突变的NSCLC患者中的潜在益处,并确定可能有助于预测治疗反应的潜在生物标志物。