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 journalArticle

22 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)815-818
Number of pages4
JournalPediatric Blood and Cancer
Volume58
Issue number5
DOIs
StatePublished - May 2012

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Amyloid Precursor Protein Secretases
Heterografts
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Neoplasms
Osteosarcoma
Disease-Free Survival
Appointments and Schedules
2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide
Growth

Keywords

  • Developmental therapeutics
  • Notch
  • Preclinical testing

ASJC Scopus subject areas

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

Cite this

Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling. / Kolb, E. Anders; Gorlick, Richard; Keir, Stephen T.; Maris, John M.; Lock, Richard; Carol, Hernan; Kurmasheva, Raushan T.; Reynolds, C. Patrick; Kang, Min H.; Wu, Jianrong; Houghton, Peter J.; Smith, Malcolm A.

In: Pediatric Blood and Cancer, Vol. 58, No. 5, 05.2012, p. 815-818.

Research output: Contribution to journalArticle

Kolb, EA, Gorlick, R, Keir, ST, Maris, JM, Lock, R, Carol, H, Kurmasheva, RT, Reynolds, CP, Kang, MH, Wu, J, Houghton, PJ & Smith, MA 2012, 'Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling', Pediatric Blood and Cancer, vol. 58, no. 5, pp. 815-818. https://doi.org/10.1002/pbc.23290
Kolb, E. Anders ; Gorlick, Richard ; Keir, Stephen T. ; Maris, John M. ; Lock, Richard ; Carol, Hernan ; Kurmasheva, Raushan T. ; Reynolds, C. Patrick ; Kang, Min H. ; Wu, Jianrong ; Houghton, Peter J. ; Smith, Malcolm A. / Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling. In: Pediatric Blood and Cancer. 2012 ; Vol. 58, No. 5. pp. 815-818.
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