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National Cancer Institute pediatric preclinical testing program: Model description for in vitro cytotoxicity testing
Author(s) -
Kang Min H.,
Smith Malcolm A.,
Morton Christopher L.,
Keshelava Nino,
Houghton Peter J.,
Reynolds C. Patrick
Publication year - 2011
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.22801
Subject(s) - medicine , neuroblastoma , pediatric cancer , cancer , in vivo , vincristine , rhabdomyosarcoma , cytotoxicity , pharmacology , etoposide , in vitro toxicology , in vitro , oncology , cancer research , chemotherapy , sarcoma , pathology , cell culture , cyclophosphamide , biology , biochemistry , genetics , microbiology and biotechnology
Abstract Background The National Cancer Institute (NCI) has established the Pediatric Preclinical Testing Program (PPTP) for testing drugs against in vitro and in vivo childhood cancer models to aid in the prioritization of drugs considered for early phase pediatric clinical trials. Procedures In vitro cytotoxicity testing employs a semi‐automated fluorescence‐based digital imaging cytotoxicity assay (DIMSCAN) that has a 4‐log dynamic range of detection. Curve fitting of the fractional survival data of the cell lines in response to various concentrations of the agents was used to calculate relative IC 50 , absolute IC 50 , and Y min values. The panel of 23 pediatric cancer cell lines included leukemia (n = 6), lymphoma (n = 2), rhabdomyosarcoma (n = 4), brain tumors (n = 3), Ewing family of tumors (EFT, n = 4), and neuroblastoma (n = 4). The doubling times obtained using DIMSCAN were incorporated into data analyses to estimate the relationship between input cell numbers and final cell number. Results We report in vitro activity data for three drugs (vincristine, melphalan, and etoposide) that are commonly used for pediatric cancer and for the mTOR inhibitor rapamycin, an agent that is currently under preclinical investigation for cancer. To date, the PPTP has completed in vitro testing of 39 investigational and approved agents for single drug activity and two investigational agents in combination with various “standard” chemotherapy drugs. Conclusions This robust in vitro cytotoxicity testing system for pediatric cancers will enable comparisons to response data for novel agents obtained from xenograft studies and from clinical trials. Pediatr Blood Cancer 2011;56:239–249. © 2010 Wiley‐Liss, Inc.