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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminopyridines / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects*
  • Drug Evaluation, Preclinical
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mice, SCID
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Aminopyridines
  • Antineoplastic Agents
  • PND 1186
  • Focal Adhesion Protein-Tyrosine Kinases