非受体酪氨酸激酶靶点在胃肠间质瘤治疗中的研究现状与进展

Advance of non-receptor tyrosine kinase targets in the treatment of gastrointestinal stromal tumor

胃肠间质瘤(gastrointestinal stromal tumor,GIST)是最常见的间叶细胞来源的胃肠肿瘤。75%~80%和10%的GIST分别存在编码受体酪氨酸激酶的KIT或PDGFRA激活突变,还有约10%的GIST不存在KIT和PDGFRA突变,称之为野生型GIST。GIST的治疗主要是以KIT及PDGFRA为靶点的受体酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)靶向治疗。然而,耐药问题一直是TKI治疗的难点和热点。野生型GIST对TKI治疗不敏感。近些年来,越来越多的研究开始关注非酪氨酸激酶靶点在GIST治疗中的潜在价值。本文对GIST分子分型及靶向治疗进行综述,着重探讨非酪氨酸激酶靶点在GIST治疗中的研究现状与进展。

Gastrointestinal stromal tumor(GIST)is the most common mesenchymal tumor of gastrointestinal tract.Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling therapeutic targets in GIST,and treatment with the KIT/PDGFRA inhibitor is the standard of care for patients with advanced GIST.Polyclonal emergence of KIT/PDGFRA secondary mutations is the main mechanism of tyrosine kinase inhibitors(TKIs)progression,making it challenging to overcome KIT/PDGFRA-inhibitor resistance.Recent years,more and more studies have focused on the potential value of non-KIT/PDGFRA tyrosine kinase targets in the treatment of GIST.This review summarizes the molecular type and targeted therapies of GIST,and focuses on the research status and advances of non-tyrosine kinase targets in the treatment of GIST.