Impact of DNA Repair Deficiency in the Evolving Treatment Landscape of Bladder Cancer.

IF 2.5 2区医学 Q2 UROLOGY & NEPHROLOGY

Current Urology Reports Pub Date : 2024-10-09 DOI:10.1007/s11934-024-01242-4

Vincent D D'Andrea, Christopher J Magnani, John Ernandez, Joaquim Bellmunt, Matthew Mossanen, Timothy N Clinton, Filipe L F Carvalho, Kent W Mouw

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Abstract

Purpose of review: 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.

Recent findings: 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.

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DNA 修复缺陷在不断变化的膀胱癌治疗中的影响。

综述的目的：本综述探讨了目前针对转移性和肌肉浸润性膀胱癌的DNA损伤反应（DDR）的治疗方法。它强调了近期将DDR抑制剂与标准化疗和免疫疗法相结合的临床试验：最近的研究结果：值得关注的研究结果包括 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手段，DDR 生物标志物筛选出的患者的无进展生存期（PFS）得到了延长。BAYOU等试验将免疫疗法与PARP抑制剂相结合，同样表明DDR生物标志物筛选出的膀胱癌患者有潜在的治疗获益。根据 DDR 相关突变特征开发保膀胱治疗方案的努力，如 RETAIN 和 HCRN 16-257 试验，迄今为止取得的结果喜忧参半。目前，人们正在努力将 DDR 抑制剂与最新的膀胱癌疗法（如抗体-药物共轭物）相结合。本综述重点介绍了在不断发展的膀胱癌治疗中，针对 DNA 修复缺陷的最新进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Urology Reports UROLOGY & NEPHROLOGY-

CiteScore

4.60

自引率

3.80%

发文量

期刊介绍： This journal intends to review the most important, recently published findings in the field of urology. By providing clear, insightful, balanced contributions by international experts, the journal elucidates current and emerging approaches to the care and prevention of urologic diseases and conditions. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as benign prostatic hyperplasia, erectile dysfunction, female urology, and kidney disease. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.