Novel Targeted Therapies for Rhabdomyosarcoma

Background
With the complete sequencing of nearly 1,000 pediatric cancer genomes, several major pediatric cancer centers are launching clinical genomics protocols to report "druggable" mutations will be reported to families and physicians. The major challenge we face today is identifying the most appropriate molecular targeted therapeutics based on the genetic lesions in a patient's tumor. In some cases, individual tumors will have multiple druggable mutations and there are no data available to help patients, their families or physicians select the most appropriate therapy. In other cases, one particular pathway may be deregulated but there may be dozens of therapeutics that are in clinical development to target that pathway.

To gain a broad understanding of the actionable genetic lesions in pediatric solid tumors, we have performed genomic analysis of over 500 pediatric solid tumors. In parallel, we have developed a protocol to develop orthotopic xenografts of the patient's tumors that have been sequenced.

Project Goal
We have now developed orthotopic xenografts of every major pediatric solid tumor including retinoblastoma, osteosarcoma, neuroblastoma, Ewing sarcoma, adrenocortical carcinoma and rhabdomyosarcoma. We have performed comprehensive molecular, cellular, molecular and genomic characterization of these xenografts to validate their origins.

The goal of this research proposal is to determine if it is feasible to use rhabdomyosarcoma orthotopic xenografts to gain insight into the most appropriate treatment for individual patients based on the genetic lesions in their tumors.