大鼠肉瘤病毒癌基因抑制剂在消化系统肿瘤中的研究进展OA

The rat sarcoma viral oncogene family(Ras)is among the most common oncogenic drivers in gastrointestinal malignancies,playing a pivotal role in colorectal cance,pancreatic ductal adenocarcinoma,and other cancers.Owing to the unique structural features of Ras proteins and the complexity of their downstream signaling networks,Ras had long been considered an"undruggable"target.In recent years,the successful approval of KRAS G12C inhibitors has broken this paradigm and accelerated the development of inhibitors targeting other mutations such as G12D,as well as pan-Ras strategies and combination therapies.However,therapeutic resistance remains a major clinical challenge.This review summarizes the mechanisms of action and clinical progress of Ras inhibitors,discusses their potential as monotherapy and in combination regimens in gastrointestinal tumors,and highlights future directions,including novel allosteric inhibitors,targeted protein degradation,and biomarker-guided strategies,with the aim of informing optimized clinical treatment.