KRAS突变型非小细胞肺癌治疗方法研究进展

The Research Progress of Treatment of KRAS Mutant Non- SmallCell Lung Cancer

KRAS基因突变是实体非小细胞肺癌(NSCLC)常见的致癌原因。由于KRAS蛋白与底物GTP具有非结合性,同时蛋白表面缺少特异性小分子抑制剂深度结合口袋等原因,一直以来,其靶点开发被认为具有极高难度。由于突变的KRAS小分子能抑制野生的KRAS活性,治疗过程中具有较大毒性以及用药不良反应。因此,目前无法对KRAS突变的NSCLC实施有效的治疗。随着G12C成为攻克KRAS突变的突破口,KRAS靶点“不可成药”历史终被改写,也引发了各大药企获批治疗药物相继上世。本文综述了近几年来KRAS突变的NSCLC在临床中比较有前景的治疗方法的应用和研究进展。

Kirsten rat sarcoma virtual oncogene homolog(KRAS)are common causes of solid non-small cell lung cancer(NSCLC)’s.Because KRAS has substrate GTP non-binding nature with a lack of specific small molecule inhibitors deep binding pockets on the protein surface,KRAS target development has always been challenging.Mutant KRAS small molecule can inhibit wild KRAS activity with greater toxicity and adverse drug reactions during treatment.Above reasons can lead to unable implementations of NSCLC treatment for KRAS mutation.G12C’s discovery is a breakthrough point in conquering KRAS mutations,in which the history of KRAS targets being‘untreatable’was eventually rewritten.This led to the approval of major pharmaceutical companies’treatment methods.The current article reviews several promising methods of KRAS mutation targeted therapy for NSCLC in clinical application and research progress in recent years.