FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity

Abstract Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and...

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Autores principales:	Simon Timbrell, Hosam Aglan, Angela Cramer, Phil Foden, David Weaver, Jonathan Pachter, Aoife Kilgallon, Robert B. Clarke, Gillian Farnie, Nigel J. Bundred
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0042b7fcefc749e8a9c051f9adcd6bb2
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spelling	oai:doaj.org-article:0042b7fcefc749e8a9c051f9adcd6bb22021-12-02T15:49:27ZFAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity10.1038/s41523-021-00263-32374-4677https://doaj.org/article/0042b7fcefc749e8a9c051f9adcd6bb22021-05-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00263-3https://doaj.org/toc/2374-4677Abstract Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival.Simon TimbrellHosam AglanAngela CramerPhil FodenDavid WeaverJonathan PachterAoife KilgallonRobert B. ClarkeGillian FarnieNigel J. BundredNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Simon Timbrell Hosam Aglan Angela Cramer Phil Foden David Weaver Jonathan Pachter Aoife Kilgallon Robert B. Clarke Gillian Farnie Nigel J. Bundred FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
description	Abstract Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival.
format	article
author	Simon Timbrell Hosam Aglan Angela Cramer Phil Foden David Weaver Jonathan Pachter Aoife Kilgallon Robert B. Clarke Gillian Farnie Nigel J. Bundred
author_facet	Simon Timbrell Hosam Aglan Angela Cramer Phil Foden David Weaver Jonathan Pachter Aoife Kilgallon Robert B. Clarke Gillian Farnie Nigel J. Bundred
author_sort	Simon Timbrell
title	FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
title_short	FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
title_full	FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
title_fullStr	FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
title_full_unstemmed	FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
title_sort	fak inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0042b7fcefc749e8a9c051f9adcd6bb2
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FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity

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