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

doi:10.1002/pbc.26304

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 journal › Article › peer-review

23 Scopus citations

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 language	English (US)
Article number	e26304
Journal	Pediatric Blood and Cancer
Volume	64
Issue number	4
DOIs	https://doi.org/10.1002/pbc.26304
State	Published - Apr 1 2017
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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10.1002/pbc.26304

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Kurmasheva, R. T., Gorlick, R., Kolb, E. A., Keir, S. T., Maris, J. M., Lock, R. B., Carol, H., Kang, M., Reynolds, C. P., Wu, J., Houghton, P. J., & Smith, M. A. (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, 64(4), Article e26304. https://doi.org/10.1002/pbc.26304

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

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abstract = "VS-4718, a novel inhibitor of focal adhesion kinase (FAK), was tested against the Pediatric Preclinical Testing Program{\textquoteright}s (PPTP{\textquoteright}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",

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

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AU - Kurmasheva, Raushan T.

AU - Gorlick, Richard

AU - Kolb, E. Anders

AU - Keir, Stephen T.

AU - Maris, John M.

AU - Lock, Richard B.

AU - Carol, Hernan

AU - Kang, Min

AU - Reynolds, C. Patrick

AU - Wu, Jianrong

AU - Houghton, Peter J.

AU - Smith, Malcolm A.

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

Abstract

Keywords

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