NIH R01 · 2025
Analyzing DNA replication and damage vulnerability in IDH mutant glioma
Project Summary Adult diffuse gliomas that harbor mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are common in younger adults, and universally evade the current aggressive therapies and remain lethal. Our team led by Co-PIs Drs. Cahill and Wakimoto have identified unique metabolic dependencies and combinatorial therapeutic strategies for IDH-mutant glioma. We have found that poly(ADP-ribose) polymerases (PARP) activation induced by the alkylating chemotherapeutic temozolomide can be therapeutically exploited by inhibition of the PAR breakdown enzyme poly(ADP-ribose) glycohydrolase (PARG), resulting in aberrant PAR accumulation and catastrophic NAD+ depletion. In…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.