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Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program

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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

PF-03084014, a γ-secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0nM to 10μM) and against the in vivo xenograft panels (administered orally twice daily on Days 1-7 and 15-21). PF-03084014 demonstrated limited in vitro activity, with no cell line achieving ≥50% inhibition. PF-03084014 induced significant differences in EFS distribution in 14 of 35 (40%) solid tumor xenografts, and 1 of 9 ALL xenografts (which lacked a NOTCH1 mutation), but objective responses were not observed. PF-03084014 demonstrated limited single agent activity in vitro and in vivo against the pediatric preclinical models studied.

Original languageEnglish
Pages (from-to)1493-1496
Number of pages4
JournalPediatric Blood and Cancer
Volume61
Issue number8
DOIs
StatePublished - Aug 2014

Funding

FundersFunder number
National Childhood Cancer Registry – National Cancer InstituteNO1-CM-42216, CA21765
National Childhood Cancer Registry – National Cancer InstituteP50CA108786

    Keywords

    • Developmental therapeutics
    • Notch inhibitors
    • Preclinical testing

    ASJC Scopus subject areas

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

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