Exploiting the Potential of Bromodomain Inhibitors in Ewing Sarcoma
Institution:
Seattle Children's Hospital
Researcher(s):
Shireen Ganapathi, MD
Grant Type:
Young Investigator Grants
Type of Childhood Cancer:
Ewing Sarcoma
Project Description:
Ewing sarcoma (ES) is an aggressive bone and soft tissue tumor affecting adolescents and young adults (AYA), and compromises about 250 pediatric and AYA cancer diagnoses yearly. With intensive therapy, survival has improved for patients with a single tumor at diagnosis, but this treatment strategy has not been effective in patients with disease present in multiple areas at diagnosis, and very few successful treatment options exist for disease that recurs following completion of initial therapy. To improve survival for these high risk ES patients, we need to streamline testing of therapeutic agents and understand further how the biology of ES leads to tumor growth and spread. Bromodomain and extraterminal domain protein (BET) inhibitors are a class of drugs that alters a specific tumors ability to turn on genes that are critical for its survival and propagation. Many tumors, including ES show striking results with BET inhibitors in the lab, but like many agents are not curative alone. Thus my proposal will identify efficacious drug combination strategies with the BET inhibitor, BMS-986158, with future goal of translating the most successful combinations to high risk patients, and identify how ES can escape BET inhibition to identify additional targets for treatment.
