晚期胃肠间质瘤药物治疗进展

Recent advances in drug therapy for advanced gastrointestinal stromal tumor

作为胃肠道较罕见的肿瘤,胃肠道间质瘤(gastrointestinal stromal tumor,GIST)的恶化率通常很高。靶向药物酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)已成为晚期GIST治疗的基石。近年来,随着新型TKI(如瑞派替尼和阿伐替尼等)相继问世,晚期GIST治疗模式已经焕然一新,GIST患者的生存期和生活质量也获得显著改善。对KIT/PDGFRA及其他基因相关通路的探索,对TKI耐药机制的深入研究,推动着TKI的更新迭代。PDGFRA的受体拮抗剂(生物制剂)、MEK抑制剂、TRK抑制剂、CDK抑制剂和免疫检查点抑制剂等新靶点、新药物的相继出现,为晚期GIST提供了更多的治疗选择,仍需进一步优化靶向治疗策略。就晚期GIST药物治疗的最新进展和未来方向进行综述。

Gastrointestinal stromal tumors(GISTs)are rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation.Tyrosine kinase inhibitors(TKIs)as targeted agents are the backbone for advanced GIST treatment.During the past years,with the unceasing emergence of new TKIs(such as ripretinib and avapritinib),the treatment paradigm of advanced GIST has dramatically changed,which also have significantly improved the survival and quality of life for patients with GIST.The discoveries of KIT/PDGFRA and other genetic pathways have led to the deeper understanding of mechanisms of TKIs and the innovations of targeted agents.The research and development of novel targets and drugs,such as PDGFRA receptor antagonists(biologics),MEK inhibitors,TRK inhibitors,CDK inhibitors and immune checkpoint inhibitors,has provided more treatment options for advanced GIST.Strategies of targeted therapy for advanced GIST will be continuously optimized.This article reviewed the recent advances and future direction of drug therapy for advanced GIST.