Abstract Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence.Focal adhesion kinase (FAK) has a role in 3m speedglas 9002nc 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 whole wheat phyllo dough (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.