CTEP Branches and Offices
NCI Pediatric Preclinical in Vivo Testing (PIVOT) Program
The NCI-supported Pediatric Preclinical in Vivo Testing (PIVOT) program systematically evaluates novel agents against genomically characterized childhood cancer solid tumor and leukemia in vivo models. The primary goal of the PIVOT program is to develop high quality preclinical data to help pediatric oncology researchers identify new agents that will show significant activity when clinically evaluated against selected childhood cancers. By supporting a more reliable agent prioritization process, the PIVOT program contributes to the goal of accelerating the discovery of more effective treatments for children with cancer. The PIVOT program testing strategy is based upon research showing that preclinical testing using genomically characterized models, when combined with knowledge about the relative drug exposures tolerated in mice and in humans, provides powerful insight into the likely clinical utility of investigational agents.
The NCI PIVOT program is supported through cooperative agreement grants to its Coordinating Center and to its Research Programs that perform the testing. PIVOT members are listed below:
| PI | Institution | Cancer Diagnoses |
|---|---|---|
| Michael A. Dyer, PhD Elizabeth Stewart, MD |
St. Jude Children’s Research Hospital | Soft tissue sarcomas including rhabdomyosarcoma |
| Richard Gorlick, MD | MD Anderson | Osteosarcoma |
| Peter Houghton, PhD Raushan Kurmasheva, PhD |
UT Health Science Center San Antonio | Ewing sarcoma rhabdomyosarcoma, kidney and liver cancers |
| Andrew Kung, MD, PhD Filemon Dela Cruz, MD |
Memorial Sloan Kettering Cancer Center | Pediatric sarcomas and other solid tumors |
| Xiao-Nan Li, MD, PhD | Ann & Robert H. Lurie Children's Hospital of Chicago | Orthotopic CNS tumors |
| Richard Lock, PhD | Children’s Cancer Inst Australia | Acute lymphoblastic leukemia |
| Yael Mosse, MD | Children’s Hospital of Philadelphia | Neuroblastoma |
| Carol Bult, PhD Jeffrey Chuang, PhD |
Jackson Laboratory | PIVOT Coordinating Center |
The PIVOT program builds upon more than 15 years of experience with the Pediatric Preclinical Testing Program (PPTP) and the Pediatric Preclinical Testing Consortium (PPTC), which collaborated with more than 80 pharmaceutical companies to test novel agents against the programs’ pediatric preclinical models. A listing of the PPTP and PPTC publications is available for review. The PPTP and PPTC found that many agents that are effective for adult cancers have limited activity against pediatric preclinical models. Activity signals were observed for some agents, including the MEK inhibitor selumetinib for BRAF-mutated glioma, the Bcl-2 inhibitor ABT-263 for acute lymphoblastic leukemia (ALL), the menin inhibitor VTP-50469 for infant ALL with KMT2A gene rearrangement, an AKR1C3-activated prodrug for T-ALL, and antibody-drug conjugates targeting surface antigens relevant to specific childhood cancers (e.g., CD19, LRRC15, and CD276/B7-H3).
For more information about the PIVOT program, contact the NCI Program Director (Dr. Malcolm Smith at Malcolm.Smith@nih.gov).