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dc.contributor.authorTimbrell, Simon
dc.contributor.authorAglan, Hosam
dc.contributor.authorCramer, Angela
dc.contributor.authorFoden, Phil
dc.contributor.authorWeaver, David
dc.contributor.authorPachter, Jonathan
dc.contributor.authorKilgallon, Aoife
dc.contributor.authorClarke, Robert B.
dc.contributor.authorFarnie, Gillian; email: gillian.farnie@ndorms.ox.ac.uk
dc.contributor.authorBundred, Nigel J.; orcid: 0000-0001-6007-056X; email: Bundredn@manchester.ac.uk
dc.date.accessioned2021-05-28T15:15:43Z
dc.date.available2021-05-28T15:15:43Z
dc.date.issued2021-05-28
dc.date.submitted2020-06-29
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624742/41523_2021_Article_263.pdf?sequence=2
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624742/41523_2021_263_MOESM1_ESM.pdf?sequence=3
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624742/41523_2021_Article_263_nlm.xml?sequence=4
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624742/41523_2021_263_MOESM2_ESM.pdf?sequence=5
dc.identifier.citationnpj Breast Cancer, volume 7, issue 1, page 65
dc.identifier.urihttp://hdl.handle.net/10034/624742
dc.descriptionFrom Springer Nature via Jisc Publications Router
dc.descriptionHistory: received 2020-06-29, accepted 2021-03-15, registration 2021-04-23, pub-electronic 2021-05-28, online 2021-05-28, collection 2021-12
dc.descriptionPublication status: Published
dc.descriptionFunder: Royal College of Surgeons of England (RCS); doi: https://doi.org/10.13039/501100000297
dc.description.abstractAbstract: 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.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsLicence for this article: http://creativecommons.org/licenses/by/4.0/
dc.sourceeissn: 2374-4677
dc.subjectArticle
dc.subject/692/4028/67/1347
dc.subject/631/154/555
dc.subject/631/532/71
dc.subjectarticle
dc.titleFAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
dc.typearticle
dc.date.updated2021-05-28T15:15:43Z
dc.date.accepted2021-03-15


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