The pediatric preclinical testing program: description of models and early testing results

Area of Science:

• Pediatric Oncology
• Cancer Therapeutics
• Preclinical Research

Background:

• The National Cancer Institute's Pediatric Preclinical Testing Program (PPTP) aims to discover new treatments for childhood cancers.
• Established xenograft and cell line panels for various pediatric malignancies, including Wilms tumor, sarcomas, neuroblastoma, brain tumors, rhabdoid tumors, and acute lymphoblastic leukemia (ALL).

Purpose of the Study:

• To characterize in vivo tumor models for pediatric cancers.
• To evaluate the efficacy of standard agents, vincristine and cyclophosphamide, in these preclinical models.

Main Methods:

• Solid tumors were grown subcutaneously in immune-deficient mice, with dimensions measured weekly.
• Acute lymphoblastic leukemia (ALL) xenografts were inoculated intravenously, and human CD45-positive cells were enumerated weekly.

Main Results:

• Vincristine showed objective responses in 25% of solid tumor models, while cyclophosphamide achieved responses in 64%.
• Tumor growth delay (TGD) measurements corroborated the high activity of both agents.
• Both vincristine and cyclophosphamide induced regressions in all evaluated ALL models.

Conclusions:

• Successfully established 51 solid tumor and 10 ALL in vivo models for preclinical testing.
• Identified vincristine and cyclophosphamide as agents with broad-spectrum activity against pediatric cancer models.
• The PPTP tumor panels show potential for identifying novel therapeutic agents with significant clinical activity.