BACKGROUND: Docetaxel, the standard chemotherapy for metastatic 
castration-resistant prostate cancer (CRPC) also enhances the survival of 
patients with metastatic castration-sensitive prostate cancer (CSPC) when 
combined with androgen-deprivation therapy. Focal Adhesion Kinase (FAK) 
activation is a mediator of docetaxel resistance in prostate cancer cells. The 
aim of this study was to investigate the effect of the second generation FAK 
inhibitor VS-6063 on docetaxel efficacy in pre-clinical CRPC and CSPC models.
METHODS: Docetaxel-resistant CRPC cells, mice with PC3 xenografts, and ex vivo 
cultures of patient-derived primary prostate tumors were treated with VS-6063 
and/or docetaxel, or vehicle control. Cell counting, immunoblotting, and 
immunohistochemistry techniques were used to evaluate the treatment effects.
RESULTS: Docetaxel and VS-6063 co-treatment caused a greater decrease in the 
viability of docetaxel-resistant CRPC cells, and a greater inhibition in PC3 
xenograft growth compared to either monotherapy. FAK expression in human primary 
prostate cancer was positively associated with advanced tumor stage. 
Patient-derived prostate tumor explants cultured with both docetaxel and VS-6063 
displayed a higher percentage of apoptosis in cancer cells, than monotherapy 
treatment.
CONCLUSIONS: Our findings suggest that co-administration of the FAK inhibitor, 
VS-6063, with docetaxel represents a potential therapeutic strategy to overcome 
docetaxel resistance in prostate cancer.