NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors

Romel Somwar et al. find that cancer-causing NTRK gene fusions resistant to one form of inhibitor therapy can be resistant to other inhibitor types. Using molecular simulations, they show that some NTRK1 mutations resistant to the type I inhibitor larotrectinib are hypersensitive to the type II inhi...

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Autores principales:	Romel Somwar, Nicolle E. Hofmann, Bryan Smith, Igor Odintsov, Morana Vojnic, Irina Linkov, Ashley Tam, Inna Khodos, Marissa S. Mattar, Elisa de Stanchina, Daniel Flynn, Marc Ladanyi, Alexander Drilon, Ujwal Shinde, Monika A. Davare
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dc4dd666029c45298c0ddd64355c90c2
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spelling	oai:doaj.org-article:dc4dd666029c45298c0ddd64355c90c22021-12-02T13:56:16ZNTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors10.1038/s42003-020-01508-w2399-3642https://doaj.org/article/dc4dd666029c45298c0ddd64355c90c22020-12-01T00:00:00Zhttps://doi.org/10.1038/s42003-020-01508-whttps://doaj.org/toc/2399-3642Romel Somwar et al. find that cancer-causing NTRK gene fusions resistant to one form of inhibitor therapy can be resistant to other inhibitor types. Using molecular simulations, they show that some NTRK1 mutations resistant to the type I inhibitor larotrectinib are hypersensitive to the type II inhibitor altiratinib, potentially due to the introduction of a sulfur moiety in the kinase binding pocket.Romel SomwarNicolle E. HofmannBryan SmithIgor OdintsovMorana VojnicIrina LinkovAshley TamInna KhodosMarissa S. MattarElisa de StanchinaDaniel FlynnMarc LadanyiAlexander DrilonUjwal ShindeMonika A. DavareNature PortfolioarticleBiology (General)QH301-705.5ENCommunications Biology, Vol 3, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Romel Somwar Nicolle E. Hofmann Bryan Smith Igor Odintsov Morana Vojnic Irina Linkov Ashley Tam Inna Khodos Marissa S. Mattar Elisa de Stanchina Daniel Flynn Marc Ladanyi Alexander Drilon Ujwal Shinde Monika A. Davare NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors
description	Romel Somwar et al. find that cancer-causing NTRK gene fusions resistant to one form of inhibitor therapy can be resistant to other inhibitor types. Using molecular simulations, they show that some NTRK1 mutations resistant to the type I inhibitor larotrectinib are hypersensitive to the type II inhibitor altiratinib, potentially due to the introduction of a sulfur moiety in the kinase binding pocket.
format	article
author	Romel Somwar Nicolle E. Hofmann Bryan Smith Igor Odintsov Morana Vojnic Irina Linkov Ashley Tam Inna Khodos Marissa S. Mattar Elisa de Stanchina Daniel Flynn Marc Ladanyi Alexander Drilon Ujwal Shinde Monika A. Davare
author_facet	Romel Somwar Nicolle E. Hofmann Bryan Smith Igor Odintsov Morana Vojnic Irina Linkov Ashley Tam Inna Khodos Marissa S. Mattar Elisa de Stanchina Daniel Flynn Marc Ladanyi Alexander Drilon Ujwal Shinde Monika A. Davare
author_sort	Romel Somwar
title	NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors
title_short	NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors
title_full	NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors
title_fullStr	NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors
title_full_unstemmed	NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors
title_sort	ntrk kinase domain mutations in cancer variably impact sensitivity to type i and type ii inhibitors
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/dc4dd666029c45298c0ddd64355c90c2
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NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors

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