NCI Pediatric Preclinical Testing Program (PPTP) Laboratories
In the Best Pharmaceuticals for Children Act (BPCA), Congress directed the National Cancer Institute (NCI) to amply and expand preclinical drug testing for childhood cancer. In response to this directive, the NCI established a consortium of institutions to carry out preclinical testing of anti-cancer drugs in both cell culture and mouse xenograft models known as the Pediatric Preclinical Testing Program (PPTP).
The overall PI for the PPTP is Peter Houghton, PhD, of St Jude's Childrens Research Hospital. The NCI project officer is Malcolm Smith, MD PhD.
The PPTP focuses on testing the most common pediatric cancers for which patients are eligible for phase I and phase II clinical trials: brain tumors, acute lyphoblastic leukemia, acute myelogenous leukemia, lymphomas, Ewing's sarcoma family tumors (ESFT), osteogenic sarcoma, brain tumors, and neuroblastoma.
The goal for the PPTP is to complete testing of one drug per month in all the xenograft panels. Drugs are batched in groups of 4 drugs tested over 4 months in the in vitro panel. Drugs are obtained under MTA from various sources by the NCI and provided to investigators in a blinded fashion for testing. The NCI determines an appropriate drug dosing for xenograft experiments and an appropriate range of concentrations for in vitro testing. In addition to new drugs, older drugs for which activity of the drug is known in patients have also been tested by the PPTP labs in a blinded fashion.
Cryopreserved banks of xenografts and cell lines are maintained by program investigators and replicates are stored at St Judes. Molecular characterization of the panel of xenografts and cell lines is being carried out by microarrays for gene expression as well as single nucleotide polymorphisms.
PPTP Laboratories
| Cell Culture Testing (all diseases) | Childrens Hospital Los Angeles |
Disease-Focused Xenograft Testing Laboratories
| ESFT, Brain tumors, rhabdomyosarcoma | St Jude's Children's Research Hospital |
| Glioblastoma | Duke University |
| Osteogenic Sarcoma | Childrens Hosp at Montefiore, Bronx,NY |
| Neuroblastoma | Children's Hospital of Philadelphia |
| Acute Lymphoblastic Leukemia | Children's Cancer Institute of Australia B |
Program Funding
NCI PPTP Grant
Laboratory Publications
- Houghton PJ, Morton CL, Tucker C, Gorlick R, Kolb EA, Zhang W, Lock R, Carol H, Reynolds CP, Keshelava N, Maris JM, Courtright J, Keir ST, Friedman HS, Stopford C, Wu J, Smith MA
Stage 1 testing of the proteasome inhibitor bortezomib by the pediatric preclinical testing program.
Pediatric Blood & Cancer (In Press, 2007) - Houghton PJ, Morton CL, Tucker C, Payne D, Favours E, Cole C, Gorlick R, Kolb EA, Zhang W, Lock R, Carol H, Tajbakhsh M, Reynolds CP, Maris JM, Courtright J, Keir ST, Friedman HS, Stopford C, Zeidner J, Wu J, Liu T, Billups CA, Khan J, Ansher S, Zhang J, Smith MA
The pediatric preclinical testing program: Description of models and early testing results.
Pediatric Blood & Cancer (In Press, 2007) - Maris JM, Courtright J, Houghton PJ, Morton CL, Gorlick R, Kolb EA, Lock R, Tajbakhsh M, Reynolds CP, Keir ST, Wu J, Smith MA
Initial testing (Stage 1) of the VEGFR inhibitor AZD2171 by the Pediatric Preclinical Testing Program.
Pediatric Blood & Cancer (In Press, 2007)