Characterization of Xenograft Models of Childhood Cancers

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This array project is being conducted in collaboration with the Children's Oncology Group (COG) Phase 1 Consortium and the Cancer Therapy Evaluation Program (CTEP) and was partially externally funded by a grant from the NCI. It is in accord with some of the requirement embodied in the Best Pharmaceuticals for Children Act which stated that the Director of the National Cancer Institute shall expand, intensify, and coordinate the activities of the Institute with respect to research on the development of preclinical models to evaluate which therapies are likely to be effective for treating pediatric cancer. There are four main objectives of this project. (1) To determine which of the currently utized pediatric cancer models (xenograft) most closely resembles the cancer(s) of origin by cDNA microarrays. (2) To develop tissue and cell microarrays and protein lysate arrays of this preclinical panel, for the purpose of identifying cancer-related molecular targets and signaling pathways that may be therapeutically exploited to improve the outcome for children that suffer from cancer. (3) To provide these tissue and protein arrays as reagents to qualified investigators in the extra- and intra-mural research community. (4) Identify xenografts that contain the same druggable mutations as those found in the human cancer. This project will facilitate pediatric cancer drug development by identifying the best xenograft models that are the most similar to the cancer of origin, and will be a resource to use in identifying molecular targets and cell signal profiles, and for subsequent testing new anti-cancer agents for their potential activity against childhood cancers. This resource has the potential to increase the pace of new therapeutic target discovery for childhood cancers and to facilitate the clinical use of new molecularly targeted agents active against childhood cancera, targets such as death pathway genes, uniquely expressed in these cancers.