DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology
Rifaquat Rahman, Diana D. Shi, Zachary J. Reitman, Petra Hamerlik, John de Groot, Daphne A. Haas‐Kogan, Alan D. D’Andrea, Erik P. Sulman, Kirk Tanner, Nathalie Y.R. Agar, Jann N. Sarkaria, Christopher L. Tinkle, Ranjit S. Bindra, Minesh P. Mehta, Patrick Y. Wen
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.