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NTRK gene fusions as novel targets of cancer therapy across multiple tumour types

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 a...

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Autores principales: Amatu, Alessio, Sartore-Bianchi, Andrea, Siena, Salvatore
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070277/
https://www.ncbi.nlm.nih.gov/pubmed/27843590
http://dx.doi.org/10.1136/esmoopen-2015-000023
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author Amatu, Alessio
Sartore-Bianchi, Andrea
Siena, Salvatore
author_facet Amatu, Alessio
Sartore-Bianchi, Andrea
Siena, Salvatore
author_sort Amatu, Alessio
collection PubMed
description 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.
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spelling pubmed-50702772016-11-14 NTRK gene fusions as novel targets of cancer therapy across multiple tumour types Amatu, Alessio Sartore-Bianchi, Andrea Siena, Salvatore ESMO Open Review 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. BMJ Publishing Group 2016-03-18 /pmc/articles/PMC5070277/ /pubmed/27843590 http://dx.doi.org/10.1136/esmoopen-2015-000023 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Review
Amatu, Alessio
Sartore-Bianchi, Andrea
Siena, Salvatore
NTRK gene fusions as novel targets of cancer therapy across multiple tumour types
title NTRK gene fusions as novel targets of cancer therapy across multiple tumour types
title_full NTRK gene fusions as novel targets of cancer therapy across multiple tumour types
title_fullStr NTRK gene fusions as novel targets of cancer therapy across multiple tumour types
title_full_unstemmed NTRK gene fusions as novel targets of cancer therapy across multiple tumour types
title_short NTRK gene fusions as novel targets of cancer therapy across multiple tumour types
title_sort ntrk gene fusions as novel targets of cancer therapy across multiple tumour types
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070277/
https://www.ncbi.nlm.nih.gov/pubmed/27843590
http://dx.doi.org/10.1136/esmoopen-2015-000023
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