NTRK gene fusions as novel targets of cancer therapy across multiple tumour types.
NTRK gene fusions as novel targets of cancer therapy across multiple tumour types.
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DOI：
10.1136/esmoopen-2015-000023
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发表时间：
2016
期刊：
影响因子：
7.3
通讯作者：
Siena S
中科院分区：
文献类型：
--
作者：
Amatu A;Sartore-Bianchi A;Siena S
原肌球蛋白受体激酶（Trk）受体家族包含3种被称为Trk A、B和C（TrkA、Trk B和TrkC）受体的跨膜蛋白，其分别由NTRK1、NTRK2和NTRK3基因编码。这些受体酪氨酸激酶在人神经元组织中表达，并通过神经营养因子的激活在神经系统发育和功能的生理学中发挥重要作用。涉及NTRK基因的基因融合导致嵌合Trk蛋白的转录，所述嵌合Trk蛋白具有赋予致癌潜力的组成型激活或过表达的激酶功能。这些遗传异常最近已经成为癌症治疗的目标，因为已经开发了新的化合物，它们是组成型活性重排蛋白的选择性抑制剂。下一代测序方法作为无偏基因融合发现的工具，正在帮助这一领域的发展。在这篇文章中，我们回顾了NTRK基因融合在几种肿瘤组织学中的作用，以及靶向这种遗传改变用于癌症治疗的前景和挑战。
The tropomyosin receptor kinase (Trk) receptor family comprises 3 transmembrane proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors that are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. These receptor tyrosine kinases are expressed in human neuronal tissue and play an essential role in the physiology of development and function of the nervous system through activation by neurotrophins. Gene fusions involving NTRK genes lead to transcription of chimeric Trk proteins with constitutively activated or overexpressed kinase function conferring oncogenic potential. These genetic abnormalities have recently emerged as targets for cancer therapy, because novel compounds have been developed that are selective inhibitors of the constitutively active rearranged proteins. Developments in this field are being aided by next generation sequencing methods as tools for unbiased gene fusions discovery. In this article, we review the role of NTRK gene fusions across several tumour histologies, and the promises and challenges of targeting such genetic alterations for cancer therapy.