DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology

Neuro Oncol. 2024 Mar 22:noae072. doi: 10.1093/neuonc/noae072. Online ahead of print.

Abstract

DNA damage response (DDR) mechanisms are critical to maintenance of overall genomic stability, and their dysfunction can contribute to oncogenesis. Significant advances in our understanding of DDR pathways have raised the possibility of developing therapies that exploit these processes. In this expert-driven consensus review, we examine mechanisms of response to DNA damage, progress in development of DDR inhibitors in IDH-wild-type glioblastoma and IDH-mutant gliomas, and other important considerations such as biomarker development, preclinical models, combination therapies, mechanisms of resistance and clinical trial design considerations.

Keywords: DDR inhibitors; DNA damage response; DNA repair; glioma; radiation therapy.