Neuroblastoma is a highly complex and aggressive pediatric cancer derived from the sympathetic nervous system that is diagnosed in approximately 500 children per year in the United States and affecting thousands of other children around the world. While neuroblastoma accounts for about 8% of all pediatric cancers in the U.S., it accounts for over 15% of all pediatric cancer related deaths.

Over the last twenty years, researchers have gained a much better understanding of neuroblastoma through both national and international efforts. Recently, encouraging developments have improved with neuroblastoma. However, these results have come at a high price through the use of highly aggressive, intensive and toxic regimens that include chemotherapy, radiation therapy, and bone marrow transplants. Unfortunately, despite these advances, the majority of children diagnosed with aggressive neuroblastoma will not survive. Therefore, more funds are needed to enhance and extend the lives of the many children who bravely wage their daily battle against neuroblastoma. Your contributions allow us to continue our commitment to support the necessary research that we hope will ultimately lead to a cure for this devastating disease.

New Approaches to Neuroblastoma Therapy

Neuroblastoma Research

Susan L. Cohn, MD

scohn@northwestern.edu

Dr. Cohn's laboratory research focuses on the biology of the pediatric cancer neuroblastoma. One research project ongoing in Dr. Cohn's laboratory involves the analysis of angiogenesis in neuroblastoma. Dr. Cohn's laboratory was the first to report the correlations between high vascular density in neuroblastoma tumors and advanced, stage disease, unfavorable histology, MYCN amplification, and poor outcome. In a subsequent paper, Dr. Cohn's team reported preclinical studies demonstrating the effectiveness of the angiogenesis inhibitor, TNP-470, in the treatment of neuroblastoma. Recently laboratory experiments indicate that the Schwann cells in neuroblastoma tumors may be producing inhibitors of angiogenesis. The laboratory is also investigating the regulation of the MYCN gene in neuroblastoma. Previous work has shown that tumor phenotype correlates with MYCN _expression levels, and that clones of the neuroblastoma cell line NBL-W differ in MYCN mRNA half-life. The laboratory received an NCI R01 to investigate the molecular mechanisms responsible for the disparity in MYCN mRNA degradation in the neuroblastoma clones. Studies performed to date have demonstrated that cis-acting sequences within the MYCN 3' untranslated region are sufficient to induce rapid mRNA degradation. Recently completed studies suggest that _expression of the ELAV-like RNA-binding protein stabilize short-live transcripts. Other studies ongoing in Dr. Cohn's laboratory include investigations of the role of DDX1, an RNA helicase that is co-amplified with the MYCN gene in neuroblastoma tumor, in determining neuroblastoma tumorigenesis, neuroblastoma apoptosis, the regulation of the multidrug related resistance-protein (MRP) in neuroblastoma, and preclinical studies examining the effectiveness of combination chemotherapy and retinoic acid in the treatment of neuroblastoma.