Brigham & Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Curr Urol Rep. 2024 Oct 9;26(1):12. doi: 10.1007/s11934-024-01242-4.
This review explores the current landscape of treatments which target the DNA damage response (DDR) in metastatic and muscle-invasive bladder cancer. It emphasizes recent clinical trials which integrate DDR inhibitors with standard chemotherapy and immunotherapy.
Noteworthy findings include the ATLANTIS trial, which demonstrated prolonged progression-free survival (PFS) in DDR biomarker-selected patients using PARP inhibitors as maintenance after standard chemotherapy. Trials such as BAYOU, which combined immunotherapy with PARP inhibition, similarly suggested a potential therapeutic benefit in DDR biomarker-selected patients with bladder cancer. Efforts to develop bladder-sparing treatment regimens based on DDR-associated mutational profiles, such as the RETAIN and HCRN 16-257 trials, have had mixed outcomes to date. There are now ongoing efforts to combine DDR inhibitors with the newest bladder cancer therapies, such as antibody-drug conjugates. This review highlights the most recent advances in targeting DNA repair deficiency in the evolving treatment landscape of bladder cancer.
本文探讨了目前针对转移性和肌层浸润性膀胱癌的 DNA 损伤反应（DDR）治疗靶点的治疗方法。强调了最近将 DDR 抑制剂与标准化疗和免疫疗法相结合的临床试验。
值得注意的发现包括 ATLANTIS 试验，该试验表明在标准化疗后，使用 PARP 抑制剂作为维持治疗，DDR 生物标志物选择的患者的无进展生存期（PFS）延长。BAYOU 等试验将免疫疗法与 PARP 抑制相结合，同样表明 DDR 生物标志物选择的膀胱癌患者可能具有潜在的治疗益处。迄今为止，基于 DDR 相关突变谱开发保膀胱治疗方案的努力，如 RETAIN 和 HCRN 16-257 试验，结果喜忧参半。目前正在努力将 DDR 抑制剂与最新的膀胱癌治疗方法（如抗体药物偶联物）相结合。本综述重点介绍了在膀胱癌治疗领域的不断发展中针对 DNA 修复缺陷的最新进展。
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