Alex's Lemonade Stand Foundation for Childhood Cancer

Mentor Name: John Prensner

Ewing sarcoma is an aggressive bone cancer that mostly affects children and teenagers. This cancer is usually caused by a genetic accident that fuses two genes, EWSR1 and FLI1, creating a new "fusion" gene called EWS-FLI1. This fusion gene acts like a faulty switch, turning on many other genes that drive the cancer's growth and make it hard to treat. Current treatments for Ewing sarcoma—like chemotherapy and surgery—are not very specific and often don't work well for patients whose cancer has spread. In our lab, we are looking for better, more targeted ways to treat this disease.

More children die from acute lymphoblastic leukemia (ALL) than any other cancer. About one-third of patients develop serious side effects (such as another cancer) as a consequence of treatment. We need to better define the molecular origins of ALL to develop new medicines that are more effective and less toxic. Many ALLs arise from T-cells. About one-third of patients with T-cell ALL carry a cancer gene called TLX1. Mice in which scientists have artificially removed the TLX1 gene are healthy. Thus, TLX1 is an attractive drug target. Blocking TLX1 should spare normal healthy tissue.

Pediatric brain tumors are the leading cause of cancer-related death in children. Children and adolescents with relapsed or refractory brain tumors have a low likelihood of long-term survival, and new therapies are desperately needed. Modifying or stimulating a patient’s immune system has been found to be a strategy to treat certain cancers, with some of these treatments even leading to cures. Unfortunately, the use of immunotherapy for many cancers, including aggressive brain tumors, has proven difficult so far for many reasons.

Ependymomas are lethal malignancies that bear a dismal prognosis and lack curative treatment strategies despite decades of research. More than 70% of childhood hemispheric ependymomas bear recurrent ZFTA-RELA fusions. Despite these advances, there are no effective treatments, targeted therapies, or clinical trials for ZFTA-RELA ependymomas. Therefore, there is a major knowledge gap and an urgent and unmet need to identify ZFTA-RELA-specific oncogenic mechanisms. Tumor cells alter nutrient uptake and utilization. This is a fundamental hallmark of cancer.