NTRK基因融合的检测及TRK抑制剂研究进展

Detection of neurotrophic tyrosine receptor kinase gene fusion and research progress of tropomyosin receptor kinase inhibitors

原肌球蛋白受体激酶(tropomyosin receptor kinase,TRK)蛋白家族由神经营养性酪氨酸受体激酶(neurotrophic tyrosine receptor kinase,NTRK)基因编码,在胚胎发育和神经系统正常功能的维持中发挥作用。已在多种成人和儿童实体瘤中确定NTRK基因融合为致癌驱动因子。NTRK基因重排和融合转录可通过不同的分子病理学技术检出,这些筛查技术为确定最可能从靶向TRK融合治疗中获益的患者提供支持。本文概述了NTRK基因融合的发生机制和特征,NTRK基因融合检测方法和检测路径,以及TRK抑制剂的治疗获益和研究进展,总结了TRK融合癌的多国共识和指南,旨在帮助临床医生了解如何和何时进行NTRK基因融合检测,以及针对TRK融合癌的靶向治疗现状,从而更好地指导患者治疗。

The tropomyosin receptor kinase(TRK)family of proteins is encoded by neurotrophic tyrosine receptor kinase(NTRK)genes and has a role in the development and normal functioning of the nervous system.NTRK gene fusions have been identified as oncogenic drivers in a wide range of tumors in both adult and pediatric patients.NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques,these screening technologies offer therapeutic supplement to identify the patients most likely to benefit from the treatments of targeting TRK fusions.In this review,we summarize the mechanism and characteristics of NTRK gene fusions,and outline the routine testing and methods of NTRK gene fusions,the therapeutic benefits and research progress of TRK inhibitors.In addition,we review the multinational consensus and guidelines for TRK fusion cancer,aiming to help clinicians understand how and when to perform NTRK fusion detection,and the current status of targeted therapy for TRK fusion cancer,so as to better guide the treatment of patients.