KRAS突变结直肠癌药物治疗的增敏策略
Sensitization Strategies for Drug Therapy in KRAS-Mutant Colorectal Cancer
DOI: 10.12677/acm.2026.162386, PDF,    科研立项经费支持
作者: 孟秋韵, 郎靖瑜, 罗 敏, 张学彬, 孟渝维, 毛 佳, 张世谱, 卿 晨*：昆明医科大学药学院暨云南省天然药物药理重点实验室，云南 昆明
关键词: KRAS突变；结直肠癌；耐药机制；治疗增敏；KRAS Mutation； Colorectal Cancer； Drug Resistance Mechanism； Therapeutic Sensitization
摘要: KRAS (kirsten rat sarcoma viral oncogene)是肿瘤高频突变基因，在结直肠癌中的突变频率超过40%。结直肠癌从癌前病变到确诊通常要经历5~10年，多数患者确诊时已处于中晚期。尽管靶向KRASG12C突变体小分子酪氨酸激酶抑制剂对KRAS突变非小细胞肺癌疗效显著，但对KRAS突变结直肠癌则疗效不佳。KRAS通路以KRAS蛋白为中枢节点，连接上游受体酪氨酸激酶(RTK)与下游效应分子，形成复杂的信号转导网络，对单一靶点的抑制可导致多种反馈和旁路激活，是现有靶向药物产生耐药的原因。本文结合本领域的相关研究成果，从KRAS突变结直肠癌对相关靶向治疗耐药的产生机制及应对策略等方面进行了综述，为克服KRAS及相关突变靶向治疗的耐药提供参考。
Abstract: KRAS (Kirsten rat sarcoma viral oncogene) is a high-frequency mutation gene in tumors, with a mutation frequency exceeding 40% in colorectal cancer (CRC). The progression from precancerous lesions to confirmed diagnosis in CRC typically takes 5 to 10 years, and most patients are diagnosed at an advanced stage. Although small-molecule tyrosine kinase inhibitors targeting the KRAS G12C mutant have shown significant efficacy in KRAS-mutant non-small cell lung cancer, their effectiveness in KRAS-mutant CRC remains limited. The KRAS pathway, with KRAS protein as its central hub, connects upstream receptor tyrosine kinases (RTKs) and downstream effector molecules, forming a complex signal transduction network. Inhibition of a single target can lead to various feedback and bypass activation mechanisms, which contribute to the development of resistance to existing targeted therapies. This review integrates relevant research achievements in the field, summarizing the mechanisms underlying resistance to targeted therapies in KRAS-mutant CRC and corresponding strategies, thereby providing insights for overcoming resistance in the targeted treatment of KRAS and related mutations
文章引用：孟秋韵, 郎靖瑜, 罗敏, 张学彬, 孟渝维, 毛佳, 张世谱, 卿晨. KRAS突变结直肠癌药物治疗的增敏策略[J]. 临床医学进展, 2026, 16(2): 244-253. https://doi.org/10.12677/acm.2026.162386

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