ALK and IGF-1R as independent targets in crizotinib resistant lung cancer

Abstract ALK positive non-small cell lung cancer is highly responsive to ALK inhibitors such as crizotinib, but drug resistance typically develops within a year of treatment. In this study we investigated whether IGF-1R is an independent druggable target in ALK-positive lung cancer cells. We confirm...

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Autores principales:	Christabel Wilson, Mhairi Nimick, Hayley Nehoff, John C. Ashton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/398999e043dc426f9106b6eb7c119b5d
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spelling	oai:doaj.org-article:398999e043dc426f9106b6eb7c119b5d2021-12-02T15:06:03ZALK and IGF-1R as independent targets in crizotinib resistant lung cancer10.1038/s41598-017-14289-w2045-2322https://doaj.org/article/398999e043dc426f9106b6eb7c119b5d2017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14289-whttps://doaj.org/toc/2045-2322Abstract ALK positive non-small cell lung cancer is highly responsive to ALK inhibitors such as crizotinib, but drug resistance typically develops within a year of treatment. In this study we investigated whether IGF-1R is an independent druggable target in ALK-positive lung cancer cells. We confirmed that combination ALK and IGF-1R inhibitor treatment is synergistically cytotoxic to ALK-positive lung cancer cells and that this remains the case for at least 12 days after initial exposure to crizotinib. ALK-positive cells with acquired resistance to crizotinib did not acquire cross-resistance to IGF-1R inhibition, though combination treatment in the resistant cells gave additive rather than synergistic cytotoxicity. We concluded that IGF-1R is an independent druggable target in ALK-positive lung cancer and support the trial of combination treatment.Christabel WilsonMhairi NimickHayley NehoffJohn C. AshtonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christabel Wilson Mhairi Nimick Hayley Nehoff John C. Ashton ALK and IGF-1R as independent targets in crizotinib resistant lung cancer
description	Abstract ALK positive non-small cell lung cancer is highly responsive to ALK inhibitors such as crizotinib, but drug resistance typically develops within a year of treatment. In this study we investigated whether IGF-1R is an independent druggable target in ALK-positive lung cancer cells. We confirmed that combination ALK and IGF-1R inhibitor treatment is synergistically cytotoxic to ALK-positive lung cancer cells and that this remains the case for at least 12 days after initial exposure to crizotinib. ALK-positive cells with acquired resistance to crizotinib did not acquire cross-resistance to IGF-1R inhibition, though combination treatment in the resistant cells gave additive rather than synergistic cytotoxicity. We concluded that IGF-1R is an independent druggable target in ALK-positive lung cancer and support the trial of combination treatment.
format	article
author	Christabel Wilson Mhairi Nimick Hayley Nehoff John C. Ashton
author_facet	Christabel Wilson Mhairi Nimick Hayley Nehoff John C. Ashton
author_sort	Christabel Wilson
title	ALK and IGF-1R as independent targets in crizotinib resistant lung cancer
title_short	ALK and IGF-1R as independent targets in crizotinib resistant lung cancer
title_full	ALK and IGF-1R as independent targets in crizotinib resistant lung cancer
title_fullStr	ALK and IGF-1R as independent targets in crizotinib resistant lung cancer
title_full_unstemmed	ALK and IGF-1R as independent targets in crizotinib resistant lung cancer
title_sort	alk and igf-1r as independent targets in crizotinib resistant lung cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/398999e043dc426f9106b6eb7c119b5d
work_keys_str_mv	AT christabelwilson alkandigf1rasindependenttargetsincrizotinibresistantlungcancer AT mhairinimick alkandigf1rasindependenttargetsincrizotinibresistantlungcancer AT hayleynehoff alkandigf1rasindependenttargetsincrizotinibresistantlungcancer AT johncashton alkandigf1rasindependenttargetsincrizotinibresistantlungcancer
_version_	1718388574921949184

ALK and IGF-1R as independent targets in crizotinib resistant lung cancer

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