Precision medicine-guided drugging of DNA repair to induce synthetic lethality in AMLs
Tomasz Skorski
PhD, MD, DScTemple University
Project Term: July 1, 2018 - June 30, 2021
We will test if Gene Expression and Mutation Analysis (GEMA) could be applied as personalized medicine tool to identify individual patients with AML displaying specific preferences for repairing spontaneous and drug-induced DNA damage. These preferences will predispose leukemia stem and progenitor cells to synthetic lethality triggered by already approved as well as novel DNA repair inhibitors.
Although tremendous progress has been made in treatment modalities of acute myeloid leukemia (AML), there is the necessity to improve and develop novel therapeutic approaches. We propose to develop a strategy based on Gene Expression and Mutation Analysis (GEMA) profiling to identify patients with AML displaying specific preferences for repairing spontaneous and drug-induced DNA damage. These pathways will be then attacked by GEMA-guided DNA repair inhibitors eventually combined with standard treatment to eliminate leukemia stem and progenitor cells without affecting normal cells and tissues.