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

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 c...

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Autores principales: Wilson, Christabel, Nimick, Mhairi, Nehoff, Hayley, Ashton, John C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654778/
https://www.ncbi.nlm.nih.gov/pubmed/29066738
http://dx.doi.org/10.1038/s41598-017-14289-w
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author Wilson, Christabel
Nimick, Mhairi
Nehoff, Hayley
Ashton, John C.
author_facet Wilson, Christabel
Nimick, Mhairi
Nehoff, Hayley
Ashton, John C.
author_sort Wilson, Christabel
collection PubMed
description 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.
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spelling pubmed-56547782017-10-31 ALK and IGF-1R as independent targets in crizotinib resistant lung cancer Wilson, Christabel Nimick, Mhairi Nehoff, Hayley Ashton, John C. Sci Rep Article 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. Nature Publishing Group UK 2017-10-24 /pmc/articles/PMC5654778/ /pubmed/29066738 http://dx.doi.org/10.1038/s41598-017-14289-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wilson, Christabel
Nimick, Mhairi
Nehoff, Hayley
Ashton, John C.
ALK and IGF-1R as independent targets in crizotinib resistant lung cancer
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654778/
https://www.ncbi.nlm.nih.gov/pubmed/29066738
http://dx.doi.org/10.1038/s41598-017-14289-w
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