Ewing's sarcoma is an aggressive bone tumor of children and young adults. Current treatment for this disease involves intensive chemotherapy, along with surgery and/or radiation therapy. These treatments are associated with serious short- and long-term side effects. Even with such intensive treatment, the overall 5-year cure rates for Ewing's sarcoma are on the order of 50%. There are two important unmet clinical needs for Ewing's sarcoma: improved diagnostic approaches to molecularly-characterize tumors, and improved therapies that target tumor-specific abnormalities.
Most cases of Ewing's sarcoma express one of a small group of abnormal genes. Most pathology labs are able to test for the most common of these abnormalities, called EWS/FLI, but not the less common. This means that some patients do not benefit from molecular testing. We propose to develop a new approach that will test for all potential abnormalities found in Ewing's sarcoma, and thus improve the diagnostic accuracy for this disease. This is important because missed diagnosis often lead to incorrect treatments being given to patients.
We have recently found that EWS/FLI causes increased levels of a second cancer-causing gene, NKX2.2. During our analyses, we identified a potential mechanism to turn-off NKX2.2 function. We now propose to look for drugs that will block NKX2.2 function, which may then be used to treat patients in the future. At the completion of these studies, we will have developed approaches that may improve the diagnosis and treatment of patients with this highly-malignant pediatric tumor.