Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling†
Corresponding Author
E. Anders Kolb MD
A.I. duPont Hospital for Children, Wilmington, Delaware
Department of Oncology, A.I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803.===Search for more papers by this authorRichard Gorlick MD
The Children's Hospital at Montefiore, Bronx, New York
Search for more papers by this authorStephen T. Keir PhD
Duke University Medical Center, Durham, North California
Search for more papers by this authorJohn M. Maris MD
Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine and Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania
Search for more papers by this authorRichard Lock PhD
Children's Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia
Search for more papers by this authorHernan Carol PhD
Children's Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia
Search for more papers by this authorRaushan T. Kurmasheva PhD
Nationwide Children's Hospital, Columbus, Ohio
Search for more papers by this authorC. Patrick Reynolds MD, PhD
Texas Tech University Health Sciences Center, Lubbock, Texas
Search for more papers by this authorMin H. Kang PharmD
Texas Tech University Health Sciences Center, Lubbock, Texas
Search for more papers by this authorJianrong Wu PhD
St. Jude Children's Research Hospital, Memphis, Tennessee
Search for more papers by this authorPeter J. Houghton PhD
Nationwide Children's Hospital, Columbus, Ohio
Search for more papers by this authorMalcolm A. Smith MD, PhD
Cancer Therapy Evaluation Program, NCI, Bethesda, Maryland
Search for more papers by this authorCorresponding Author
E. Anders Kolb MD
A.I. duPont Hospital for Children, Wilmington, Delaware
Department of Oncology, A.I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803.===Search for more papers by this authorRichard Gorlick MD
The Children's Hospital at Montefiore, Bronx, New York
Search for more papers by this authorStephen T. Keir PhD
Duke University Medical Center, Durham, North California
Search for more papers by this authorJohn M. Maris MD
Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine and Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania
Search for more papers by this authorRichard Lock PhD
Children's Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia
Search for more papers by this authorHernan Carol PhD
Children's Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia
Search for more papers by this authorRaushan T. Kurmasheva PhD
Nationwide Children's Hospital, Columbus, Ohio
Search for more papers by this authorC. Patrick Reynolds MD, PhD
Texas Tech University Health Sciences Center, Lubbock, Texas
Search for more papers by this authorMin H. Kang PharmD
Texas Tech University Health Sciences Center, Lubbock, Texas
Search for more papers by this authorJianrong Wu PhD
St. Jude Children's Research Hospital, Memphis, Tennessee
Search for more papers by this authorPeter J. Houghton PhD
Nationwide Children's Hospital, Columbus, Ohio
Search for more papers by this authorMalcolm A. Smith MD, PhD
Cancer Therapy Evaluation Program, NCI, Bethesda, Maryland
Search for more papers by this authorConflict of interest: Nothing to declare.
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. Pediatr Blood Cancer 2012; 58: 815–818. © 2011 Wiley Periodicals, Inc.
Supporting Information
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| pbc_23290_sm_SupplTab.doc287.5 KB | Supplementary Table |
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