Inhibition of the RNA translation factor, eIF4E, as a novel treatment strategy in Ewing Sarcoma
Dr. John Prensner, M.D., Ph.D. – The Regents of the University of Michigan, Ann Arbor, MI
Ewing sarcoma is a rare, aggressive bone cancer mainly affecting children and young adults. Patients with metastatic or recurrent forms face poor prognoses, with 5-year survival rates dropping to 15-30 percent. Treatment involves aggressive chemotherapy and clinical trials exploring innovative therapies, though recent trials have not notably improved outcomes. Current research focuses on the cancer’s biological foundations, specifically the EWSR1-FLI1 fusion protein, which hijacks normal RNA processes to propagate the cancer. Our lab targets RNA translation, the process of making proteins from RNA, as a potential treatment avenue in pediatric cancers like Ewing sarcoma. Our preliminary data show that Ewing sarcoma cells are particularly sensitive to drugs impeding RNA translation. Key components of RNA processing are abundant in these cancer cells, presenting an opportunity for novel therapies. This proposal hypothesizes that blocking EIF4E, a critical component of RNA translation, could effectively treat Ewing sarcoma. Utilizing resources at the University of Michigan, we aim to test both existing and new drugs targeting EIF4E. Our research will involve assessing the efficacy of these drugs on Ewing sarcoma models and tumors in mice, as well as exploring the molecular reasons behind the cancer's susceptibility. This work seeks to deepen our understanding of Ewing sarcoma's cancer biology while identifying small molecule inhibitors suitable for clinical development.
