Development of Transporter Targeted Platinum Drugs for Pediatric Tumor

Project Summary/Abstract Childhood cancers remain a leading cause of death in children between 1 and 14 years of age. Of the childhood cancers, solid tumors are among the least curable. The goal of the proposed Phase I studies will be to develop targeted anti-cancer platinum analogs to treat three childhood tumors: osteosarcoma, rhabdomyosarcoma and neuroblastoma. In the U.S. about 1600 children are diagnosed with these tumors each year with about 400 to 800 dying each year from these diseases. Cisplatin, afirst generation platinum analog, together with other drugs are used in the treatment of these solid tumors. However, cisplatin is highly toxic and causes irreversible kidney damage and hearing loss, which is especially devastating in children because itresults in lifelong difficulties in communication and learning. Moreover, high doses of cisplatin, which may be curative, cannot be administered, because of the toxicities. The three childhood cancers selected for the proposed studies have high expression