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The pediatric preclinical testing program: Description of models and early testing results
Author(s) -
Houghton Peter J.,
Morton Christopher L.,
Tucker Chandra,
Payne Debbie,
Favours Edward,
Cole Claire,
Gorlick Richard,
Kolb E. Anders,
Zhang Wendong,
Lock Richard,
Carol Hernan,
Tajbakhsh Mimi,
Reynolds C. Patrick,
Maris John M.,
Courtright Joshua,
Keir Stephen T.,
Friedman Henry S.,
Stopford Charles,
Zeidner Joseph,
Wu Jianrong,
Liu Tiebin,
Billups Catherine A.,
Khan Javed,
Ansher Sherry,
Zhang Jian,
Smith Malcolm A.
Publication year - 2007
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21078
Subject(s) - rhabdomyosarcoma , medulloblastoma , medicine , in vivo , vincristine , neuroblastoma , wilms' tumor , ependymoma , cyclophosphamide , osteosarcoma , sarcoma , preclinical testing , pediatric cancer , cancer research , cancer , oncology , pharmacology , pathology , chemotherapy , cell culture , biology , genetics , microbiology and biotechnology , medical physics
Background The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panels of childhood cancer xenografts and cell lines to be used for in vivo and in vitro testing. These include panels for Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, and medulloblastoma), rhabdoid tumors (CNS and renal), and acute lymphoblastic leukemia (ALL). Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide. Procedures Solid tumors were grown subcutaneously in immune‐deficient mice and tumor dimensions were measured weekly. ALL xenografts were inoculated intravenously and human CD45‐positive cells were enumerated weekly. Results Vincristine‐induced objective responses in 6 of 24 (25%) and cyclophosphamide‐induced objective responses in 18 of 28 (64%) solid tumor models. Comparable assessments of high levels of activity for these two agents were obtained using a tumor growth delay (TGD) measure. Both agents induced regressions in each of the ALL models evaluated. Conclusions We have established 51 solid tumor and 10 ALL in vivo models. The models identify vincristine and cyclophosphamide as having broad‐spectrum activity. The PPTP tumor panels appear to generally recapitulate the activity of these agents against specific childhood cancers and to have the potential for identifying novel agents having significant clinical activity. Pediatr Blood Cancer 2007;49:928–940. Published 2006 Wiley‐Liss, Inc.