Gene-mediated therapy for BCG-unresponsive nonmuscle-invasive bladder cancer: mechanisms, clinical evidence, and practical implementation.

IF 2.2 3区 医学 Q2 UROLOGY & NEPHROLOGY
Current Opinion in Urology Pub Date : 2025-11-01 Epub Date: 2025-09-18 DOI:10.1097/MOU.0000000000001345
Chris Ho-Ming Wong, David Ka-Wai Leung, Paolo Gontero, Jeremy Yuen-Chun Teoh
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引用次数: 0

Abstract

Purpose of review: Gene therapy has emerged as an attractive bladder-sparing strategy for patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC), addressing a therapeutic gap for those ineligible for or declining radical cystectomy. This review aims to describe the recent advances in gene-mediated therapies for BCG-unresponsive NMIBC.

Recent findings: The bladder's unique anatomy with direct intravesical access and capacity for high local exposure with minimal systemic absorption provides an ideal context for gene delivery. Advances in barrier modulation with Syn3 and vector engineering have enabled efficient delivery. Adenoviral vectors as illustrated by the FDA-approved nadofaragene firadenovec (Adstiladrin), and other platforms, such as the conditionally replicating oncolytic adenoviruses (cretostimogene, CG0070), are maturing. Combination regimens of gene therapy and immune checkpoint inhibitors have shown additive or synergistic activity, deepening durability of gene therapy. Novel advancements including urinary and plasma tumor DNA are emerging as predictive biomarkers to guide patient selection, monitor minimal residual disease, and trigger early salvage.

Summary: Gene-mediated therapy is gradually advancing NMIBC care, with expanding indications and potent combinations positing itself to improve bladder preservation and long-term outcomes.

基因介导治疗bcg无反应的非肌肉浸润性膀胱癌:机制、临床证据和实际实施。
综述目的:基因治疗已成为一种有吸引力的保膀胱策略,用于高风险、卡介苗(BCG)无反应的非肌肉浸润性膀胱癌(NMIBC)患者,解决了那些不符合条件或正在接受根治性膀胱切除术的患者的治疗缺口。本文综述了基因介导治疗bcg无应答的NMIBC的最新进展。最近的研究发现:膀胱独特的解剖结构具有直接膀胱内通路和高局部暴露和最小全身吸收的能力,为基因传递提供了理想的环境。Syn3和矢量工程的阻挡调制技术的进步使高效传输成为可能。腺病毒载体如fda批准的nadofaragene firadenovec (Adstiladrin)和其他平台,如有条件复制的溶瘤腺病毒(cretostimogene, CG0070),正在成熟。基因治疗和免疫检查点抑制剂的联合治疗方案显示出附加或协同作用,加深了基因治疗的持久性。包括尿液和血浆肿瘤DNA在内的新进展正在成为指导患者选择、监测最小残留疾病和触发早期抢救的预测性生物标志物。摘要:基因介导治疗正在逐步推进NMIBC的治疗,适应症的扩大和有效的联合治疗有望改善膀胱保存和长期预后。
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 Opinion in Urology
Current Opinion in Urology 医学-泌尿学与肾脏学
CiteScore
5.00
自引率
4.00%
发文量
140
审稿时长
6-12 weeks
期刊介绍: ​​​​​​​​Current Opinion in Urology delivers a broad-based perspective on the most recent and most exciting developments in urology from across the world. Published bimonthly and featuring ten key topics – including focuses on prostate cancer, bladder cancer and minimally invasive urology – the journal’s renowned team of guest editors ensure a balanced, expert assessment of the recently published literature in each respective field with insightful editorials and on-the-mark invited reviews.
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