# Advances in Diagnosis and Targeted Therapy of KRASG12C Mutant Non-small Cell Lung Cancer

## TL;DR

This paper reviews advances in diagnosing and treating KRASG12C mutant non-small cell lung cancer, focusing on detection methods and targeted therapies.

## Contribution

The paper provides a comprehensive overview of current diagnostic techniques and emerging targeted therapies for KRASG12C mutations in NSCLC.

## Key findings

- PCR and sequencing are primary methods for detecting KRAS mutations, with varying performance and throughput.
- Approved KRASG12C inhibitors like sotorasib and adagrasib show clinical efficacy in treating NSCLC.
- Combination therapies with KRASG12C inhibitors and other drugs are being explored to overcome resistance and improve outcomes.

## Abstract

肺癌是全球范围内癌症相关死亡的首要原因，对人类健康构成重大威胁。非小细胞肺癌（non-small cell lung cancer, NSCLC）患者中，Kirsten鼠类肉瘤病毒癌基因（Kirsten rat sarcoma viral oncogene, KRAS）突变是重要的致癌驱动因素，其中KRASG12C突变是最常见的亚型之一。目前，KRAS突变的检测方法主要集中在聚合酶链式反应（polymerase chain reaction, PCR）及测序平台，两类平台所衍生出的多种技术在检测性能和检测通量等方面各有优劣，并在组织活检及液体活检领域具有重要应用价值。在靶向治疗方面，索托拉西布、阿达格拉西布、氟泽雷塞、格索雷塞、戈来雷塞等KRASG12C靶向药物在临床试验中展现出一定疗效，先后获批应用于临床。为克服靶向药物的耐药性，改善患者获益，靶向药物与化疗、免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）、Src同源2结构域蛋白酪氨酸磷酸酶2（Src homology region 2 domain-containing phosphatase 2, SHP2）抑制剂、表皮生长因子受体（epidermal growth factor receptor, EGFR）单克隆抗体等药物的联合治疗策略不断涌现。本文系统回顾了KRASG12C突变NSCLC的诊断及靶向治疗进展，旨在为临床治疗策略的选择及后续研究提供参考。

Comparison of major diagnostic techniques for KRAS mutation

Safety and efficacy of approved KRASG12C targeted drugs in KRASG12C mutated NSCLC

Safety and efficacy of other KRASG12C targeted drugs in KRASG12C mutated NSCLC

Efficacy and safety of KRASG12C targeted drugs in combination with other drugs in NSCLC