Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling

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

doi:10.1002/pbc.23290

Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling

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

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

RO4929097 is a potent and selective inhibitor of γ-secretase and as a result is able to inhibit Notch pathway signaling. The activity of RO4929097 was evaluated against the in vivo panels of the Pediatric Preclinical Testing Program (PPTP). RO4929097 induced significant differences in event-free survival (EFS) distribution compared to control in 6 of 26 (23%) of the evaluable solid tumor xenografts and in 0 of 8 (0%) of the evaluable ALL xenografts. The most consistent tumor growth delay effects were noted in the osteosarcoma panel. RO4929097 at the dose and schedule evaluated demonstrated little antitumor activity against childhood cancer xenografts.

Original language	English (US)
Pages (from-to)	815-818
Number of pages	4
Journal	Pediatric Blood and Cancer
Volume	58
Issue number	5
DOIs	https://doi.org/10.1002/pbc.23290
State	Published - May 2012
Externally published	Yes

Keywords

Developmental therapeutics
Notch
Preclinical testing

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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10.1002/pbc.23290

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Kolb, E. A., Gorlick, R., Keir, S. T., Maris, J. M., Lock, R., Carol, H., Kurmasheva, R. T., Reynolds, C. P., Kang, M. H., Wu, J., Houghton, P. J., & Smith, M. A. (2012). Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling. Pediatric Blood and Cancer, 58(5), 815-818. https://doi.org/10.1002/pbc.23290

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abstract = "RO4929097 is a potent and selective inhibitor of γ-secretase and as a result is able to inhibit Notch pathway signaling. The activity of RO4929097 was evaluated against the in vivo panels of the Pediatric Preclinical Testing Program (PPTP). RO4929097 induced significant differences in event-free survival (EFS) distribution compared to control in 6 of 26 (23%) of the evaluable solid tumor xenografts and in 0 of 8 (0%) of the evaluable ALL xenografts. The most consistent tumor growth delay effects were noted in the osteosarcoma panel. RO4929097 at the dose and schedule evaluated demonstrated little antitumor activity against childhood cancer xenografts.",

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year = "2012",

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doi = "10.1002/pbc.23290",

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AU - Kolb, E. Anders

AU - Gorlick, Richard

AU - Keir, Stephen T.

AU - Maris, John M.

AU - Lock, Richard

AU - Carol, Hernan

AU - Kurmasheva, Raushan T.

AU - Reynolds, C. Patrick

AU - Kang, Min H.

AU - Wu, Jianrong

AU - Houghton, Peter J.

AU - Smith, Malcolm A.

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AB - RO4929097 is a potent and selective inhibitor of γ-secretase and as a result is able to inhibit Notch pathway signaling. The activity of RO4929097 was evaluated against the in vivo panels of the Pediatric Preclinical Testing Program (PPTP). RO4929097 induced significant differences in event-free survival (EFS) distribution compared to control in 6 of 26 (23%) of the evaluable solid tumor xenografts and in 0 of 8 (0%) of the evaluable ALL xenografts. The most consistent tumor growth delay effects were noted in the osteosarcoma panel. RO4929097 at the dose and schedule evaluated demonstrated little antitumor activity against childhood cancer xenografts.

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Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling

Abstract

Keywords

ASJC Scopus subject areas

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