title: Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program.
abstract: VS-4718, a novel inhibitor of focal adhesion kinase (FAK), was tested against the Pediatric Preclinical Testing Program's (PPTP's) in vitro cell line panel and showed a median relative IC50of 1.22 μM. VS-4718 was tested in vivo against the PPTP xenograft models using a dose of 50 mg/kg administered by the oral route twice daily for 21 days. VS-4718 induced significant differences in an event-free survival distribution compared with control in 18 of 36 of the evaluable solid tumor xenografts and in 0 of 8 acute lymphoblastic leukemia (ALL) xenografts, but no xenograft lines showed tumor regression. Future plans include further evaluation of the role of FAK inhibition in combination with ABL kinase inhibitors for Ph+ALL.
authors: Nationwide Children's Hospital, Center for Childhood Cancer and Blood Diseases, Columbus, Ohio.
authors: Raushan T
authors: RT
authors: Kurmasheva
authors: The Children's Hospital at Montefiore, D.I.duPont Hospital for Children, Department of Oncology, Wilmington, Delaware.
authors: Richard
authors: R
authors: Gorlick
authors: A.I. duPont Hospital for Children, Wilmington, Delaware.
authors: E Anders
authors: EA
authors: Kolb
authors: Duke University Medical Center, Department of Surgery, Durham, North Carolina.
authors: Stephen T
authors: ST
authors: Keir
authors: Children's Hospital of Philadelphia, Hematology-Oncology, Philadelphia, Pennsylvania.
authors: John M
authors: JM
authors: Maris
authors: Children's Cancer Institute Australia, Leukemia Biology Program, Randwick, NSW, Australia.
authors: Richard B
authors: RB
authors: Lock
authors: Children's Cancer Institute Australia, Leukemia Biology Program, Randwick, NSW, Australia.
authors: Hernan
authors: H
authors: Carol
authors: Texas Tech University Health Sciences Center, Cancer Center, Lubbock, Texas.
authors: Min
authors: M
authors: Kang
authors: Texas Tech University Health Sciences Center, Cancer Center, Lubbock, Texas.
authors: C Patrick
authors: CP
authors: Reynolds
authors: St.Jude Children's Research Hospital, Biostatistics, Memphis, Tennessee.
authors: Jianrong
authors: J
authors: Wu
authors: Nationwide Children's Hospital, Center for Childhood Cancer and Blood Diseases, Columbus, Ohio.
authors: Peter J
authors: PJ
authors: Houghton
authors: Cancer Therapy Evaluation Program, NCI, Bethesda, Maryland.
authors: Malcolm A
authors: MA
authors: Smith
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; C559284:PND 1186; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: VS-4718; developmental therapeutics; focal adhesion kinase (FAK); preclinical testing