MEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance

Colorectal cancer cells can acquire resistance to MEK inhibition due to BRAF or KRAS amplification. Here, the authors show that while MEK inhibitor withdrawal in BRAF mutant cells restores sensitivity to the inhibitor through the loss of BRAF amplification mediated by a p57-dependent mechanism, drug...

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Autores principales:	Matthew J. Sale, Kathryn Balmanno, Jayeta Saxena, Eiko Ozono, Katarzyna Wojdyla, Rebecca E. McIntyre, Rebecca Gilley, Anna Woroniuk, Karen D. Howarth, Gareth Hughes, Jonathan R. Dry, Mark J. Arends, Pilar Caro, David Oxley, Susan Ashton, David J. Adams, Julio Saez-Rodriguez, Paul D. Smith, Simon J. Cook
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/2c81d11afd5f46b09ea78ec188faf540
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spelling	oai:doaj.org-article:2c81d11afd5f46b09ea78ec188faf5402021-12-02T16:57:21ZMEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance10.1038/s41467-019-09438-w2041-1723https://doaj.org/article/2c81d11afd5f46b09ea78ec188faf5402019-05-01T00:00:00Zhttps://doi.org/10.1038/s41467-019-09438-whttps://doaj.org/toc/2041-1723Colorectal cancer cells can acquire resistance to MEK inhibition due to BRAF or KRAS amplification. Here, the authors show that while MEK inhibitor withdrawal in BRAF mutant cells restores sensitivity to the inhibitor through the loss of BRAF amplification mediated by a p57-dependent mechanism, drug withdrawal from KRAS mutant cells does not restore sensitivity but results in EMT and chemoresistance.Matthew J. SaleKathryn BalmannoJayeta SaxenaEiko OzonoKatarzyna WojdylaRebecca E. McIntyreRebecca GilleyAnna WoroniukKaren D. HowarthGareth HughesJonathan R. DryMark J. ArendsPilar CaroDavid OxleySusan AshtonDavid J. AdamsJulio Saez-RodriguezPaul D. SmithSimon J. CookNature PortfolioarticleScienceQENNature Communications, Vol 10, Iss 1, Pp 1-22 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Matthew J. Sale Kathryn Balmanno Jayeta Saxena Eiko Ozono Katarzyna Wojdyla Rebecca E. McIntyre Rebecca Gilley Anna Woroniuk Karen D. Howarth Gareth Hughes Jonathan R. Dry Mark J. Arends Pilar Caro David Oxley Susan Ashton David J. Adams Julio Saez-Rodriguez Paul D. Smith Simon J. Cook MEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance
description	Colorectal cancer cells can acquire resistance to MEK inhibition due to BRAF or KRAS amplification. Here, the authors show that while MEK inhibitor withdrawal in BRAF mutant cells restores sensitivity to the inhibitor through the loss of BRAF amplification mediated by a p57-dependent mechanism, drug withdrawal from KRAS mutant cells does not restore sensitivity but results in EMT and chemoresistance.
format	article
author	Matthew J. Sale Kathryn Balmanno Jayeta Saxena Eiko Ozono Katarzyna Wojdyla Rebecca E. McIntyre Rebecca Gilley Anna Woroniuk Karen D. Howarth Gareth Hughes Jonathan R. Dry Mark J. Arends Pilar Caro David Oxley Susan Ashton David J. Adams Julio Saez-Rodriguez Paul D. Smith Simon J. Cook
author_facet	Matthew J. Sale Kathryn Balmanno Jayeta Saxena Eiko Ozono Katarzyna Wojdyla Rebecca E. McIntyre Rebecca Gilley Anna Woroniuk Karen D. Howarth Gareth Hughes Jonathan R. Dry Mark J. Arends Pilar Caro David Oxley Susan Ashton David J. Adams Julio Saez-Rodriguez Paul D. Smith Simon J. Cook
author_sort	Matthew J. Sale
title	MEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance
title_short	MEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance
title_full	MEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance
title_fullStr	MEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance
title_full_unstemmed	MEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance
title_sort	mek1/2 inhibitor withdrawal reverses acquired resistance driven by brafv600e amplification whereas krasg13d amplification promotes emt-chemoresistance
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/2c81d11afd5f46b09ea78ec188faf540
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MEK1/2 inhibitor withdrawal reverses acquired resistance driven by BRAFV600E amplification whereas KRASG13D amplification promotes EMT-chemoresistance

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