Uncovering the Contribution of RNA Binding Proteins to Neuroblastoma Aggression

Emory University – Winship Cancer Institute, Atlanta, GA

High-risk neuroblastoma is an extremely aggressive pediatric cancer of the developing sympathetic nervous system. Unfortunately, fewer than 50% of patients survive and survivors experience multiple treatment-related side effects, including decreased growth/development, bone damage, and an increased risk of developing other cancers. Thus, novel targets and therapies must be developed for this disease.

This study focuses on a poorly characterized class of proteins known as RNA binding proteins (RBPs). These proteins bind RNA, which contains the direct instructions to make proteins (proteins carry out many key functions in cells). We have now discovered that the RBP, Musashi 2 (MSI2), is highly expressed in neuroblastoma, causing uncontrollable growth. We will determine how MSI2 causes neuroblastoma to act aggressively, studying its function in cell line and animal models and determining other signaling networks with which MSI2 communicates. MSI2 constitutes a promising drug target and our studies will help build the initial foundation for potentially drugging this protein directly or indirectly. In addition, there are approximately 1550 other RBPs and we will use a “high-throughput” technique that will allow us, for the first time, to determine how RBPs contribute to neuroblastoma aggression. We believe that our focused studies on MSI2 as well as our more global studies on the 1550 other RBPs will nominate new therapeutic targets for this aggressive disease.