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Neuroblastoma (NB), a cancer that commonly affects young children, often presents with aggressive clinical behavior and poor prognosis, making the identification of effective therapeutic targets essential. NB is known for its resistance to conventional chemotherapy, and one of the mechanisms contributing to this resistance is the activation of a key regulator of gene expression, known as 'NF-kB’. NF-kB activates the expression of genes that contribute to NB survival. NF-kB also plays a role in promoting spread of NB to other parts of the body (e.g. bone marrow, liver, and lymph nodes). Because of its critical role in regulating survival, inflammation, and metastasis, NF-kB presents an attractive target for novel therapeutic strategies in NB. Inhibition of the NF-kB pathway can potentially sensitize NB cells to chemotherapy, reduce tumor growth, and inhibit metastasis. Dr. Letterio and colleagues will explore the activity of a new class of drugs (known as SOTs), that are potent inhibitors of NF-kB.

This grant is named for David's Warriors, a St. Baldrick's Hero Fund. The fund was created in memory of David Heard who battled neuroblastoma until his passing at the age of ten. David inspired his family and countless others to commit to raising money for research to fight pediatric cancer through the St. Baldrick’s Foundation. The Fund honors the amazing spirit with which he lived, embracing life until the very end.

T-lymphoblastic leukemia is a blood cancer with a higher rate of chemo-resistance and central nervous system involvement than B cell leukemia. Dr. Letterio's research utilizes models and molecular biology techniques to test how a novel molecular target controls the development of acute T-lymphoblastic leukemia in the bone marrow and the central nervous system. Success in this new area of research will offer new hope in the development of novel therapies against T-cell leukemia.

Lymphoblasts infiltrate the central nervous system (CNS) in about 30% of children and adolescents with acute lymphoblastic leukemia (ALL), leading to relapse in the brain and spinal cord. While aggressive CNS therapy involving high-dose chemotherapy with radiation has been successful, many patients have significant problems with long-term effects, including a much higher risk of a second cancer and long-term deficits in cognitive function and development. This research is to discover unique aspects of the biology and pathogenesis of leukemia, with a goal of finding new therapeutic targets that can be tested in future clinical trials.  

This grant helps provide necessary resources at this institution to ensure that more kids can be treated on clinical trials, their best hope for a cure.

This grant helps provide necessary resources at this institution to ensure that more kids can be treated on clinical trials, their best hope for a cure.