Efficacy and Safety of KRASG12C Inhibitors in Advanced Solid Tumors with KRASG12C-mutated: A Single-arm Meta-analysis / 肿瘤防治研究

Objective To systematically study the efficacy and safety of KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated. Methods Computer searches from PubMed, The Cochrane Library, Web of Science, Embase, CNKI, and CBM databases were conducted to collect clinical studies on KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated, with a search time from inception to October 12, 2022. Then, two investigators independently screened the literature, extracted information, assessed the risk of bias in included studies, and performed meta-analyses using RevMan 5.4 software. Results There were four publications included, all of which were single-arm clinical studies. The KRASG12C inhibitors that completed clinical phase Ⅰ and Ⅱ trials were sotorasib and adagrasib, with two publications each. A total of 388 and 394 patients were included in the efficacy evaluation and safety evaluation, respectively. Resultsof the Meta-analysis showed that the patients had objective response rate, overall disease control, and disease stabilization rates of 35%, 82%, and 45%, respectively. In addition, the rate of serious adverse events, general adverse events, and all adverse events in patients was 2%, 28%, and 79%, respectively. Moreover, the rate of partial remission of disease in NSCLC patients was 38%. Conclusion The KRASG12C inhibitors sotorasib and adagrasib exhibited good efficacy and high safety in advanced solid tumors.

Research progress on the drug resistance mechanism and coping strategies of KRASG12C inhibitor for non-small cell lung cancer / 中国肿瘤生物治疗杂志

@#[摘 要] 鼠类肉瘤病毒癌基因（KRAS）是非小细胞肺癌（NSCLC）中最常见的致癌基因之一，由于KRAS蛋白表面相对平滑，缺少可结合小分子的药物口袋，长期以来被视为“不可用药的靶点”。最近针对KRASG12C基因点突变的靶向药物相继在临床研究中取得了一定进展，特别是KRASG12C特异性抑制剂阿达格拉西布（adagrasib）和索托拉西布（sotorasib）的应用给NSCLC患者治疗带来了希望。携带KRAS基因突变的肿瘤具有巨大的肿瘤异质性，且KRASG12C抑制剂存在明显的耐药问题，其机制可能与KRAS基因的二次突变或扩增、旁路激活和组织学转化等有关。KRAS基因参与多种调节细胞生存和增殖的信号通路，了解其耐药机制对开发可能的治疗策略应对耐药至关重要。KRASG12C共价抑制剂与免疫抑制剂及各靶向药物联用现已相继进入临床试验，将有效增强和推动KRASG12C共价抑制剂在NSCLC治疗中的应用。

Apoptosis-inducing activity of synthetic hydrocarbon-stapled peptides in H358 cancer cells expressing KRAS

Lung cancers are the leading cause of cancer deaths worldwide and pose a grave threat to human life and health. Non-small cell lung cancer (NSCLC) is the most frequent malignancy occupying 80% of all lung cancer subtypes. Except for other mutations (