Project: Identification of novel targeted agents for alveolar rhabdomyosarcoma
Sole Benefactor: Jacob Koenigs ‘Jakefest’ Memorial Fund
Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents. One sub-type of rhabdomyosarcoma, called alveolar rhabdomyosarcoma (ARMS), has a particularly poor prognosis. Many children have metastatic disease (cancer that has spread throughout the body) at diagnosis and only 50% of children diagnosed with ARMS will survive five years.
The current era of targeted molecular medicine promises to make significant advances in treating both childhood and adult cancers. However, because rhabdomyosarcoma is a rare cancer, there are obstacles to new drug discovery. One of these obstacles is the mapping and screening of genes involved in children’s cancer. In order to develop a targeted treatment, researchers need to know what genes are involved in the cancer’s development, how to target them, and what compounds effectively reach the disease.
Ranjit Bindra, MD, PhD, at Yale University, was recently awarded a CureSearch Young Investigator grant for his work identifying novel targeted drugs for ARMS. Dr. Bindra’s project has three primary steps. First, his team will perform a large-scale screen for drugs that target a particular mutation that leads to rhabdomyosarcoma. This step involves screening over 100,000 drug compounds that might effectively target PAX3/7-FOX01, the “fusion gene” that results from the chromosome mutating in a cancer cell. The second step is confirming “drug hits.” This step involves examining the entire genome of ARMS in order to identify new targets. Finally, the work will involve validating these “hits” in a cell line panel. This step confirms that drugs will effectively destroy ARMS tumors.
Dr. Bindra hopes to publish the results of his genetic research and drug screenings so that academic and industry partners can use them for further research and drug development. Academic projects like Dr. Bindra’s are crucial for the development of novel therapeutics for children’s cancers, especially less common cancers like ARMS. His research promises to stimulate further drug discovery with the ultimate goal of delivering new medications that can be used to treat ARMS and other rare cancers.