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Pediatr Blood Cancer. 2017 Apr;64(4). doi: 10.1002/pbc.26304. Epub 2016 Oct 27.

Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program.

Author information

1
Nationwide Children's Hospital, Center for Childhood Cancer and Blood Diseases, Columbus, Ohio.
2
The Children's Hospital at Montefiore, D.I.duPont Hospital for Children, Department of Oncology, Wilmington, Delaware.
3
A.I. duPont Hospital for Children, Wilmington, Delaware.
4
Duke University Medical Center, Department of Surgery, Durham, North Carolina.
5
Children's Hospital of Philadelphia, Hematology-Oncology, Philadelphia, Pennsylvania.
6
Children's Cancer Institute Australia, Leukemia Biology Program, Randwick, NSW, Australia.
7
Texas Tech University Health Sciences Center, Cancer Center, Lubbock, Texas.
8
St.Jude Children's Research Hospital, Biostatistics, Memphis, Tennessee.
9
Cancer Therapy Evaluation Program, NCI, Bethesda, Maryland.

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 IC50 of 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.

KEYWORDS:

VS-4718; developmental therapeutics; focal adhesion kinase (FAK); preclinical testing

PMID:
27786412
PMCID:
PMC5578428
DOI:
10.1002/pbc.26304
[Indexed for MEDLINE]
Free PMC Article

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