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

Raushan T. Kurmasheva, Richard Gorlick, E. Anders Kolb, Stephen T. Keir, John M. Maris, Richard B. Lock, Hernan Carol, Min Kang, C. Patrick Reynolds, Jianrong Wu, Peter J Houghton, Malcolm A. Smith

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere26304
JournalPediatric Blood and Cancer
Volume64
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Focal Adhesion Protein-Tyrosine Kinases
Heterografts
Pediatrics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms
Inhibitory Concentration 50
Disease-Free Survival
Phosphotransferases
Cell Line
PND 1186

Keywords

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

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program. / Kurmasheva, Raushan T.; Gorlick, Richard; Kolb, E. Anders; Keir, Stephen T.; Maris, John M.; Lock, Richard B.; Carol, Hernan; Kang, Min; Reynolds, C. Patrick; Wu, Jianrong; Houghton, Peter J; Smith, Malcolm A.

In: Pediatric Blood and Cancer, Vol. 64, No. 4, e26304, 01.04.2017.

Research output: Contribution to journalArticle

Kurmasheva, RT, Gorlick, R, Kolb, EA, Keir, ST, Maris, JM, Lock, RB, Carol, H, Kang, M, Reynolds, CP, Wu, J, Houghton, PJ & Smith, MA 2017, 'Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program', Pediatric Blood and Cancer, vol. 64, no. 4, e26304. https://doi.org/10.1002/pbc.26304
Kurmasheva, Raushan T. ; Gorlick, Richard ; Kolb, E. Anders ; Keir, Stephen T. ; Maris, John M. ; Lock, Richard B. ; Carol, Hernan ; Kang, Min ; Reynolds, C. Patrick ; Wu, Jianrong ; Houghton, Peter J ; Smith, Malcolm A. / Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program. In: Pediatric Blood and Cancer. 2017 ; Vol. 64, No. 4.
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