KRAS是西方国家非鳞状非小细胞肺癌（NSCLC）中最常见的突变致癌基因。在各种KRAS突变体中，KRAS G12C是最常见的变异体（约40%），在非鳞状非小细胞肺癌中占10-13%。最近，KRAS G12C选择性抑制剂sotorasib和adagrasib获得了对于携带KRAS G12C的晚期或转移性NSCLC患者的治疗批准，将KRAS转变为可治疗的靶点。在本综述中，我们探讨了KRAS在晚期NSCLC中从预后标志物到预测标志物的不断演变的作用，讨论了KRAS G12C的生物学特性、现实世界中的患病率、共突变的临床相关性以及分子检测的方法。现实世界的证据表明，在晚期NSCLC中，不同地理区域的KRAS G12C患病率存在显著差异（美国为8.9-19.5%，欧洲为9.3-18.4%，拉丁美洲为6.9-9.0%，亚洲为1.4-4.3%）此外，关于KRAS G12C共突变如STK11、KEAP1和TP53的临床数据也在不断增加。现实世界的证据表明，KRAS G12C突变NSCLC与STK11、KEAP1和TP53共突变分别在10.3-28.0%、6.3-23.0%和17.8-50.0%的患者中相关联。虽然sotorasib和adagrasib目前只被批准用于晚期/转移性NSCLC的第二线治疗以及更进一步的治疗，但在进行第一线治疗之前，应该将KRAS G12C变异体的检测和报告纳入常规生物标志物检测中。KRAS G12C测验结果应在患者的健康记录中进行清楚的记录，以便在进展中采取行动。如有条件，建议使用下一代测序技术进行同时测试可能可行的生物标志物，以节约组织。通过分子检测的结果应该指导对KRAS G12C突变的晚期NSCLC患者的临床决策。版权所有© 2023作者。由Elsevier B.V.出版。保留所有权利。

KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (NSCLC) in Western countries. Of the various KRAS mutants, KRAS G12C is the most common variant (~40%), representing 10-13% of advanced non-squamous NSCLC. Recent regulatory approvals of the KRASG12C-selective inhibitors sotorasib and adagrasib for patients with advanced or metastatic NSCLC harboring KRASG12C have transformed KRAS into a druggable target. In this review, we explore the evolving role of KRAS from a prognostic to a predictive biomarker in advanced NSCLC, discussing KRAS G12C biology, real-world prevalence, clinical relevance of co-mutations, and approaches to molecular testing. Real-world evidence demonstrates significant geographic differences in KRAS G12C prevalence (8.9-19.5% in the US, 9.3-18.4% in Europe, 6.9-9.0% in Latin America, and 1.4-4.3% in Asia) in advanced NSCLC. Additionally, the body of clinical data pertaining to KRAS G12C co-mutations such as STK11, KEAP1, and TP53 is increasing. In real-world evidence, KRAS G12C-mutant NSCLC was associated with STK11, KEAP1, and TP53 co-mutations in 10.3-28.0%, 6.3-23.0%, and 17.8-50.0% of patients, respectively. Whilst sotorasib and adagrasib are currently approved for use in the second-line setting and beyond for patients with advanced/metastatic NSCLC, testing and reporting of the KRAS G12C variant should be included in routine biomarker testing prior to first-line therapy. KRAS G12C test results should be clearly documented in patients' health records for actionability at progression. Where available, next-generation sequencing is recommended to facilitate simultaneous testing of potentially actionable biomarkers in a single run to conserve tissue. Results from molecular testing should inform clinical decisions in treating patients with KRAS G12C-mutated advanced NSCLC.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.