胃肠道间质瘤的分子学机制及靶向治疗

C-kit/PDGFRA基因发生功能获得性突变和因此引发的KIT蛋白自主磷酸化是胃肠道间质瘤(gastrointestinal stromal tumors,GISTs)发生过程中最具特征性的分子机制.这一发现使得imatinib靶向治疗GISTs成为可能并取得重大疗效,但研究发现不同类型的GISTs对imatinib治疗的反应也不尽相同,并且随着其临床应用的增加,耐药性及不良反应也随之出现,迫使imatinib临床停药或改为二线用药.因此,GISTs是由不同生物学机制引发的一组疾病,本文就GISTs的分子生物学机制及靶向治疗药物作一综述.

Gastrointestinal stromal tumors: Molecular pathogenesis and targeted therapy

The autophosphorylation of KIT protein, resulting from gain-of-function mutations of the c-kit or PDGFR gene, is the most important molecular mechanism involved in the pathogenesis of gastrointestinal stromal tumors (GISTs). Imatinib is a small molecule tyrosine kinase inhibitor and is effective in the treatment of GISTs. KIT is a convenient target in GISTs, and inhibition of this receptor with imatinib (Gleevec, STI571) in GISTs has shown dramatic efficacy. Unfortunately, resistance to imatinib is a significant clinical problem. Further understanding of the molecular pathogenesis of GISTs is therefore important and may lead to the identification of novel drug targets. This review will focus on recent advances in the understanding of molecular mechanisms involved in the pathogenesis of all types of GISTs. The molecular biological characteristics of each type of GISTs will also be discussed.