National Cancer Institute pediatric preclinical testing program: Model description for in vitro cytotoxicity testing

Min H. Kang, Malcolm A. Smith, Christopher L. Morton, Nino Keshelava, Peter J. Houghton, C. Patrick Reynolds

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

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 IC50, absolute IC50, and Ymin 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.

Original languageEnglish (US)
Pages (from-to)239-249
Number of pages11
JournalPediatric Blood and Cancer
Volume56
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Keywords

  • Cell line models
  • Childhood cancer
  • Cytotoxicity
  • DIMSCAN
  • NCI PPTP

ASJC Scopus subject areas

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

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