The PPTP is an NCI initiative to address the challenge facing pediatric oncology researchers of reliably prioritizing new agents for study in children with cancer. The PPTP will systematically test 10-15 new agents annually against in vitro and in vivo preclinical models of childhood cancers, with testing ideally occurring near the time that the agents are entering testing in humans and prior to their initial evaluation in children. The PPTP’s in vivo tumor panels include xenograft lines for sarcomas (rhabdomyosarcoma and Ewing sarcoma) (n=8), neuroblastoma (n=6), osteosarcoma (n=6), acute lymphoblastic leukemia (n=8), brain tumors (n=4 glioblastoma, n=6 non-glioblastoma), and kidney cancers (n=6). Stage 1 in vivo testing will occur at the tested agent’s MTD. Agents will also be tested against the PPTP in vitro panel, which includes 24 cell lines representing a variety of childhood cancers. Those agents that demonstrate sufficient activity (either broad-spectrum or histiotype specific) in Stage 1 testing will be considered for Stage 2 testing. Stage 2 testing will define dose response relationships using tumor models in which activity was observed in Stage 1 and will include detailed pharmacokinetic and pharmacodynamic studies to establish the relationship between systemic exposure and antitumor activity. Stage 2 testing may also include evaluation in appropriate secondary models (e.g., orthotopically implanted tumors) to confirm or refute results obtained using subcutaneous tumors. Genetically engineered mouse models may also be utilized when relevant models are available. The PPTP xenograft and cell lines are being molecularly characterized, including gene expression profiling using both cDNA and Affymetrix arrays, and LOH and chromosome copy number assessment using the Affymetrix GeneChip 10K array. Tissue arrays and protein lysate arrays will be available for documenting protein expression. Initial gene expression results using cDNA arrays confirm the close relationship between the xenograft models and their respective cancers of origin. Results obtained by the PPTP will be correlated with the clinical activity and the pharmacokinetic profile of the tested agents in children to assess the predictive capabilities of the PPTP’s childhood cancer panels. If successful, the PPTP will markedly facilitate the selection of appropriate agents for clinical evaluation.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]