Emory University Archives - Hyundai Hope On Wheels

2019

Young Investigator

Jenny Shim

Atlanta, GA

Executive Summary: Neuroblastoma is the most common extra-cranial solid tumor of childhood. Despite intense multimodal therapy, more than half of patients with high-risk neuroblastoma relapse with aggressive chemotherapy-resistant disease, stressing an unmet need for therapies targeting and/or preventing recurrent disease. Relapsed neuroblastoma tumors display significantly more genetic alterations than at diagnosis, including findings of increased Yes-Associated Protein (YAP) activity, also found to contribute to poor patient outcomes. YAP is a protein that regulates genes promoting cell growth, cell self-renewal, and cell survival. Thus, YAP has been implicated in many tumor types but the role of YAP in neuroblastoma is not well characterized. We have shown that YAP is present in many well characterized cell lines derived from relapsed human neuroblastoma tumors. Moreover, we find that in patient tumor samples, YAP is present in post-therapy or recurrent tumors, but not at diagnosis. Therefore, we seek to understand the role of YAP in neuroblastoma recurrence and relapsed disease especially in the setting of tumor cell formation and initiation. We will also identify novel drug combinations through a drug screening platform to develop therapy regimens to target YAP in high-risk and recurrent neuroblastoma.
The goal of these investigations is to define YAP’s role in neuroblastoma recurrence and to further our understanding of relapsed neuroblastoma pathogenesis. Ultimately, we will prioritize identifying and validating novel combination therapies targeting YAP and cooperating tumor pathways to treat patients with the most difficult to cure disease—those with recurrent/refractory high-risk neuroblastoma. Importantly, YAP plays a role in many other cancers and through these investigations, our hope is that these novel therapy regimens will be applicable to other high risk cancers in addition to neuroblastoma.

The goals of this project are:
– To determine the role of the Yes-Associated Protein in neuroblastoma tumor formation and recurrence
– To identify and validate new drug combinations for targeting YAP in high-risk and recurrent neuroblastoma