title: Sunitinib and PF-562,271 (FAK/Pyk2 inhibitor) effectively block  growth and recovery of human hepatocellular carcinoma in a rat  xenograft model.
abstract: METHODS
  To investigate the antitumor effect of sunitinib and FAK/Pyk2 tyrosine kinase inhibitor (PF-562,271)combination therapy in vivo, utilizing human hepatocellular carcinoma (HCC) cells Huh7.5. Nude rats were inoculated subcutaneously with Huh7.5 hepatoma cells. Dosing for Phase 1 was initiated on day 5 post tumor inoculations with Vehicle(Group 1), sunitinib (25 mg/kg/day; Group 2) and sunitinib plus PF-562,271 combination (15 mg/kg/day; Group 3). Phase 2 of the study started on day 26, and each of the three original groups was divided in two subgroups; half of the rats remained on original therapy (Groups 1A and 2A) with the exception of Group 3A that was euthanized after Phase 1. The other half of the rats were switched to sunitinib and PF-562,271 combination (Group 1B) or vehicle (Groups 2B and 3B). Tumor volume and weight, serum alpha feto-protein (AFP), contrast-enhanced ultrasound imaging (CEUS) and tumor histology were used to evaluate effects of treatment on tumor growth.
  
  
  RESULTS
  The results from this study indicate that the combination of sunitinib and PF-562,271 TKI has the potential to target different aspects of angiogenesis and tumor aggressiveness and may have significantly greater effect than relevant single agent, blocking not only tumor growth, but also impacting the ability of the tumor to recover upon withdrawal of the therapy.
authors.affiliation: Global Science & Technology, PGRD, Pfizer, Inc., Groton, CT 06340, USA. cedo.bagi@pfizer.com
authors.forename: Cedo M
authors.initials: CM
authors.lastname: Bagi
authors.forename: James
authors.initials: J
authors.lastname: Christensen
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Cohen
authors.forename: Walter G
authors.initials: WG
authors.lastname: Roberts
authors.forename: Dean
authors.initials: D
authors.lastname: Wilkie
authors.forename: Terri
authors.initials: T
authors.lastname: Swanson
authors.forename: Theresa
authors.initials: T
authors.lastname: Tuthill
authors.forename: Catharine J
authors.initials: CJ
authors.lastname: Andresen
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051418:Focal Adhesion Kinase 2 / Q000037:antagonists & inhibitors; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011923:Rats, Nude; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D000077210:Sunitinib; D023041:Xenograft Model Antitumor Assays
chemical_list: D007211:Indoles; C527797:N-methyl-N-(3-((2-(2-oxo-2,3-dihydro-1H-indol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino)-methyl)-pyridin-2-yl)-methanesulfonamide; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D013449:Sulfonamides; D051418:Focal Adhesion Kinase 2; D000077210:Sunitinib