Most pediatric low-grade brain tumors harbor a specific change in their DNA that promotes tumor growth. This DNA change creates a fusion between two genes, the first is a gene (called BRAF) that is already known to promote tumor growth, and the second is a poorly characterized gene. Drugs have been developed which block this fusion gene, but these drugs still have several challenges when they are used to treat patients. The first problem is that many patients are initially resistant to the drugs, which necessitates devising alternative treatment strategies.

Pediatric acute myeloid leukemia (AML) is an aggressive cancer of the blood that despite very intense treatment can be very difficult to cure. In particular, a subset of AML characterized by genetic changes affecting a protein called MECOM have very poor outcomes. MECOM is also a critical regulator of normal blood stem cells that helps maintain stem cells throughout an individual?s life. High MECOM levels in AML confer stem-cell like properties to AML cells and make them more resistant to standard treatment and more likely to relapse.

Ewing sarcoma is an aggressive cancer usually diagnosed in teenagers. When this cancer advances and spreads to other parts of the body (metastasizes), it is very difficult to cure. Patients with metastatic Ewing sarcoma often receive radiation to help treat the cancer. During radiation therapy, the body?s immune system can help attack cancer cells. However, sometime this effect is suppressed. We are working to understand immune cell suppression during radiation with the hope that by reactivating the immune system, we can improve treatment response.

Despite intensive treatment, about half of all children with high-risk neuroblastoma die of their disease. These aggressive tumors often have a mutated MYCN gene, which drives tumor cell growth by helping them to produce the necessary building blocks for DNA, proteins, and polyamines. Polyamines are essential chemicals created from amino acids like proline and arginine that enable cells to grow and to survive. Tumors with high levels of polyamines behave aggressively and can resist treatment.

Neuroblastoma is a childhood cancer that forms from the developing nervous system. Like many cancers, there is a wide range of long-term outcomes for neuroblastoma. For patients diagnosed with high-risk disease, treatment is intensive and includes surgery, chemotherapy, and radiation. Despite this aggressive treatment, approximately one half of all high-risk patients are not cured by current approaches. Many high-risk, treatment resistant tumors demonstrate activation of the MYCN gene. There is a gap in our ability to treat cancers driven by MYCN.