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

Abstract

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 2 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.

• Authors: Haihao Sun, Stephen Pisle, Erin R Gardner, William D Figg
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 10 Issue 1 Pg. 38-43 (Jul 01 2010) ISSN: 1555-8576 [Electronic] United States
• PMID: 20495381 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Indoles
• N-methyl-N-(3-((2-(2-oxo-2,3-dihydro-1H-indol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino)-methyl)-pyridin-2-yl)-methanesulfonamide
• Sulfonamides
• Focal Adhesion Protein-Tyrosine Kinases

Topics

• Animals
• Focal Adhesion Protein-Tyrosine Kinases (antagonists & inhibitors)
• Humans
• Indoles (pharmacology)
• Injections, Subcutaneous
• Luminescent Measurements
• Lymphatic Metastasis
• Male
• Mice
• Mice, Nude
• Phosphorylation (drug effects)
• Prostatic Neoplasms (drug therapy, enzymology, pathology)
• Sulfonamides (pharmacology)
• Survival Rate
• Xenograft Model Antitumor Assays