FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity
Clarke, Robert B
Bundred, Nigel J
AffiliationBreast Biology Group, Manchester Breast Centre, Oglesby Cancer Research Building, University of Manchester, Manchester,
MetadataShow full item record
AbstractCancer 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.
CitationTimbrell S, Aglan H, Cramer A, Foden P, Weaver D, Pachter J, et al. FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity. npj Breast Cancer. 2021 May 28;7(1).
JournalNPJ Breast Cancer
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