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KRAS突变肿瘤的药物治疗研究进展
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Abstract:
KRAS突变是肺癌、结直肠癌、胰腺癌等多种实体肿瘤的关键驱动事件，不同突变亚型在生物学行为和治疗反应上呈现高度异质性。针对KRAS突变肿瘤的药物治疗主要包括靶向治疗、免疫治疗等。KRASG12C抑制剂的问世标志着靶向治疗取得突破性进展，非G12C亚型、泛KRAS及相关信号通路的干预药物也在持续研发中，免疫治疗同样展现出临床应用潜力。然而，单一疗法的疗效受多种因素限制，整合多靶点、多通路抑制并联合免疫治疗的策略正成为重要的发展方向。文章围绕KRAS突变的肺癌、结直肠癌和胰腺癌，对药物靶向治疗、免疫治疗及联合治疗的研究进展进行综述，并总结应用进展、面临挑战及新兴疗法，以期为促进KRAS突变肿瘤药物治疗发展提供参考。
KRAS mutation serves as a critical oncogenic driver event in multiple solid tumors, including lung cancer, colorectal cancer, and pancreatic cancer. Different KRAS mutation subtypes exhibit high heterogeneity in biological behavior and therapeutic response. Pharmacological interventions for KRAS-mutant tumors primarily comprise targeted therapy and immunotherapy. The development of KRASG12C inhibitors has marked a breakthrough in targeted therapy, while therapeutic strategies targeting non-G12C subtypes, pan-KRAS, and related signaling pathways are advancing. Immunotherapy has also demonstrated clinical potential. Nevertheless, the efficacy of monotherapy is constrained by multiple factors. The combination therapy integrating multi-target, multi-pathway inhibition with immunotherapy has emerged as a direction. This article reviews the advances, challenges, and emerging therapies in targeted therapy, immunotherapy, and combination therapy for KRAS-mutant tumors, aiming to facilitate the development of pharmacological treatments.
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