Bioluminescent imaging study: FAK inhibitor, PF-562,271, preclinical study in PC3M-luc-C6 local implant and metastasis xenograft models

Focal adhesion kinase (FaK) is essential in regulating integrin signaling pathways responsible for cell survival and proliferation, as well as motility, making FaK a distinctive target in the field of anticancer drug development, especially with regards to metastatic disease.¹ Our objective was to demonstrate tumor growth inhibition by pF-562,271, a selective inhibitor of FaK and FaK2, or pyk2,² in mouse xenograft models, both subcutaneous and metastatic, employing the human prostate cancer cell line pC3M-luc-C6, a modified pC3M cell line that expresses luciferase. after two weeks of treatment with pF-562,271, 25 mg/kg pO BID 5x/wk, the subcutaneous model showed a 62% tumor growth inhibition compared to control based on tumor measurements (p < 0.05), with a 88% vs. a 490% increase in bioluminescent signal for treatment and control respectively (p < 0.05). In the metastasis model, the percent change from baseline, after 18 days of treatment, of the treatment group was 2,854% vs. 14,190% for the vehicle (p < 0.01). These results show that pF-562,271 has a potent effect on metastatic prostate cancer growth in vivo.