Investigating the Role of the RNA Binding Protein LIN28 in Neuroblastoma
Neuroblastoma is the most frequent extra-cranial solid tumor in children, accounting for almost 10% of all childhood cancers and close to 15% of childhood cancer deaths. Amplification of the MYCN gene occurs in up to 40% of neuroblastomas, which results in very high levels of MYCN protein and is a marker of very poor prognosis. Current treatment strategies for MYCN amplified tumors are ineffective and in desperate need of new therapeutic avenues. Successful disruption of MYCN function in neuroblastoma would be an exciting therapeutic breakthrough and would save lives. We have discovered a novel protein that controls MYCN in high risk neuroblastoma. The LIN28B protein helps maintain high levels of MYCN protein in neuroblastoma cells. Without LIN28B, MYCN protein levels drop and the cells lose their ability to cause tumors. The aims in this proposal outline an approach to capitalize on both the LIN28B/MYCN relationship and LIN28B regulation to discover new drug targets for the treatment of poor prognosis neuroblastoma patients. Indeed, one of the aims is to study several candidate proteins that might be needed in order for LIN28B to support MYCN pro-cancer activity. Successful completion of this aim will identify the first therapeutic target for disruption of the LIN28B/MYCN pathway in neuroblastoma. LIN28B probably supports MYCN activity through its ability to control RNA is cells. Studying a protein like LIN28B represents a new way to think about therapy for neuroblastoma by trying to target the MYCN 'support network' within a cancer cell.
For the latest information on this study, please read this article published online by Nature in July, 2016.