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 ngetikin 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 here inhibition with adjuvant therapy has the potential to improve breast cancer survival.