Preclinical evaluation of omacetaxine as a novel therapeutic for ATRT
Dr. John Prensner, M.D., Ph.D. – University of Michigan Medical Center (Michigan Medicine), Ann Arbor, MI
Children with atypical teratoid/rhabdoid tumor (ATRT), an aggressive brain cancer mainly afflicting infants and toddlers, frequently relapse and die from disease, despite receiving intensive treatment. As such, developing rational and effective therapeutic approaches for ATRT is a pressing clinical need. Unfortunately, extensive efforts to study ATRT have not shown genetic alterations that are readily targetable with therapeutic agents. Therefore, to achieve better treatments for children with ATRT, new therapeutic approaches based on the biology of this disease are needed. We have found that ATRT cells exhibit an exaggerated reliance on the cellular process of protein translation, which is how cancer cells convert genetic material (DNA and RNA) into functional proteins that perform cellular jobs. Moreover, protein translation is targetable, and one drug, named omacetaxine, is already used in adult cancer patients with leukemia. We have found that omacetaxine is highly effective at killing ATRT cells. The purpose of this grant is to evaluate this omacetaxine for the treatment of mouse models of ATRT. We hypothesize that treatment with omacetaxine will result in increased survival for mouse models of ATRT. Thus, successful completion of this proposal will provide the pre-clinical data necessary to support a clinical trial testing omacetaxine in children. Our overall goal is to translate the findings of this research into a clinical trial within the next 3-4 years.
