Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA.
Neuro Oncol. 2024 Aug 5;26(8):1367-1387. doi: 10.1093/neuonc/noae072.
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.
DNA 损伤反应 (DDR) 机制对于维持整体基因组稳定性至关重要，其功能障碍可能导致肿瘤发生。我们对 DDR 途径的理解的重大进展提高了开发利用这些过程的治疗方法的可能性。在本次专家主导的共识性综述中，我们研究了对 DNA 损伤的反应机制、在 IDH 野生型胶质母细胞瘤和 IDH 突变型胶质瘤中开发 DDR 抑制剂的进展，以及其他重要考虑因素，如生物标志物开发、临床前模型、联合治疗、耐药机制和临床试验设计考虑。
