Understanding why neuroblastoma tumours become resistant to treatment
Neuroblastoma is responsible for 15% of pediatric cancer deaths. While patient survival is high for low and intermediate-risk patients, over 60% of children diagnosed with high-risk neuroblastoma do not survive past the age of 5. High-risk in neuroblastoma is often associated with amplification (increased copies) of a cancer-causing gene called MYCN. DEAD box proteins are involved in all cellular functions related to RNA, and hence play a significant role in cell survival. Previous research undertaken by the Godbout lab indicates that the DEAD Box 1 (DDXl) gene is amplified along with the MYCN gene in about 50% of high-risk neuroblastoma. The goal of this research project is to investigate the role of DDXl in neuroblastoma cell survival. To do this, we will compare the survival of neuroblastoma cells treated with various agents used in the clinic for the treatment of neuroblastoma patients: radiation, doxorubicin and vincristine. We will use neuroblastoma cells that have MYCN amplification, and neuroblastoma cells that have both MYCN and DDXl amplification, to examine the effect of DDXl overexpression on neuroblastoma cell survival. We will also use an experimental approach called immunoprecipitation to identify the proteins that interact with DDXl in neuroblastoma cells. This will help us deduce the cellular pathways through which DDXl acts in neuroblastoma cells. Through this research, we will gain an understanding of how neuroblastoma cells become resistant to treatment which is critical for the development of more effective treatments for children with high-risk neuroblastoma.