Shu Chun-Lu, Liu Yu-Ling
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, People's Republic of China.
Department of Medical Laboratory Science, Fenyang College of Shanxi Medical University, Feiyang, Shanxi, 032200, People's Republic of China.
Cancer Manag Res. 2022 Dec 16;14:3485-3492. doi: 10.2147/CMAR.S387665. eCollection 2022.
To summarize the targeted therapies and immunotherapy of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant non-small cell lung cancer (NSCLC), and discuss the ongoing clinical trials.
KRAS mutations occur in about 30% of patients with NSCLC and are the second most frequent genetic variation in lung cancer. It has been considered "undruggable" for 40 years until the discovery of a direct inhibitor of KRAS G12C. The promising direct KRAS G12C inhibitors such as sotorasib and MRTX849 have made a breakthrough with promising anti-tumor effects in patients with KRAS G12C-mutant advanced/metastatic NSCLC post one prior line of therapy. Following the success of immune checkpoint inhibitors (ICIs) in NSCLC, many patients harboring KRAS mutations can benefit from ICIs. However, due to disease heterogeneity, the prognosis of patients remains unsatisfactory, leaving room for personalized treatment options, such as new targeted therapies and other therapies.
In this review, we aim to dissect the strategies of clinical trials in these tumors, shifting from a few chemotherapy options to targeted and immunotherapy, in the context of molecular selection of KRAS-mutant NSCLC subtypes.
总结 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）突变的非小细胞肺癌（NSCLC）的靶向治疗和免疫治疗，并讨论正在进行的临床试验。
KRAS 突变发生在约 30%的 NSCLC 患者中，是肺癌中第二常见的基因变异。在发现 KRAS G12C 的直接抑制剂之前，它被认为“不可成药”达 40 年之久。索托拉西布和 MRTX849 等有前景的直接 KRAS G12C 抑制剂已取得突破，在接受过一线治疗的 KRAS G12C 突变晚期/转移性 NSCLC 患者中具有有前景的抗肿瘤作用。继免疫检查点抑制剂（ICI）在 NSCLC 中取得成功之后，许多携带 KRAS 突变的患者可从 ICI 中获益。然而，由于疾病的异质性，患者的预后仍不尽人意，这为个性化治疗方案（如新型靶向治疗和其他治疗）留出了空间。
在本综述中，我们旨在剖析这些肿瘤的临床试验策略，即在 KRAS 突变 NSCLC 亚型的分子选择背景下，从少数化疗方案转向靶向治疗和免疫治疗。
