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

ABSTRACT: RO4929097 is a potent and selective inhibitor of ?-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.

SUBMITTER: Kolb EA

PROVIDER: S-EPMC3276746 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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

Kolb E Anders EA Gorlick Richard R Keir Stephen T ST Maris John M JM Lock Richard R Carol Hernan H Kurmasheva Raushan T RT Reynolds C Patrick CP Kang Min H MH Wu Jianrong J Houghton Peter J PJ Smith Malcolm A MA

Pediatric blood & cancer 20110816 5

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 ...[more]

PMID: 22052798

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