RAS相关通路介导的结直肠癌药物联合治疗的应用

RAS相关信号通路在结直肠癌的发生、发展中起着重要作用，与该类肿瘤细胞的增殖、转移、凋亡密切相关。目前，包括靶向药物、化疗药物的单药治疗对结直肠癌的临床获益并不理想。近年来，在临床试验和临床前研究中RAS相关信号通路的抑制剂与其他药物的联合应用取得了良好效果，其中EGFR抑制剂、VEGF抑制剂、RAS直接抑制剂、MEK抑制剂和RAF抑制剂的表现尤为突出。本文就RAS相关信号通路与结直肠癌的作用关系、临床试验和临床前研究中的联合用药策略以及组合用药的耐药机制研究进行系统性综述，以期为未来临床多药治疗策略奠定基础。

Drug Combination Therapy for RAS-related Colorectal Cancer

RAS-related signaling system plays an important role in the occurrence and development of colorectal cancer, which is closely related to the proliferation, metastatic potential, and apoptosis of colorectal cancer cells. However, treating this type of cancer with a single medicine, either targeted therapies or chemotherapies, is not always the best option. In recent years, RAS-related signaling pathway inhibitors have been utilized in conjunction with other medications with promising outcomes in clinical trials and preclinical investigations. When used in concert with other anti-cancer drugs, EGFR inhibitors, VEGF inhibitors, RAS direct inhibitors, MEK inhibitors, and RAF inhibitors have shown particularly impressive performance. In terms of clinical value, combining cetuximab with chemotherapy regimens, EGFR inhibitors with chemotherapy regimens, and EGFR inhibitors with other anti-cancer drugs dramatically enhanced important indicators in patients with colorectal cancer who had wild-type RAS. However, treatment options for patients with RAS-mutant colorectal cancer have been less favorable, and in this context, anti-angiogenic and anti-EGFR agents and immune checkpoint inhibitors have been approved as second-line treatment options. In preclinical studies, inhibitors that directly target RAS have been shown to be effective in combination with other drugs, and other treatment options have also shown good results, giving patients with colorectal cancer unlimited hope. This review focuses on the relationship between RAS-related signaling pathways and colorectal cancer, combination tactics in clinical trials and preclinical studies, and research on drug resistance mechanisms linked with composition administration in order to lay the foundation for future clinical multidrug therapy strategies.