Zhang Fei, Li Sheng
Department of Urology Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China.
Department of Anorectal Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China.
Front Immunol. 2025 May 13;16:1591191. doi: 10.3389/fimmu.2025.1591191. eCollection 2025.
Antibody-drug conjugates (ADCs) have emerged as a transformative therapeutic modality in oncology, offering unprecedented precision in targeting tumor cells while sparing healthy tissues. In bladder cancer, a malignancy with high recurrence rates and limited treatment options, ADCs have demonstrated remarkable efficacy by targeting specific tumor-associated antigens such as NECTIN-4 and Human Epidermal Growth Factor Receptor 2 (HER2). This review provides a comprehensive evaluation of the current landscape of ADC-based therapies for bladder cancer, focusing on their mechanisms of action, clinical efficacy, and safety profiles.
We systematically analyze 232 clinical trials from 2004 to 2025, revealing a significant upward trend in ADC research, particularly following the Food and Drug Administration's (FDA) accelerated approval of Enfortumab vedotin in 2019.
Our findings highlight the predominance of HER2, NECTIN4, and PD-1 as the most extensively studied molecular targets, with a growing interest in combining ADCs with immune checkpoint inhibitors. Geographically, the United States and China lead in ADC clinical trials, reflecting robust research investment and infrastructure.
espite the promising advancements, challenges such as toxicity management, patient stratification, and trial design remain critical. This review underscores the importance of continued innovation in ADC technology and personalized approaches to overcome these limitations, ultimately paving the way for more effective and safer treatment options for bladder cancer patients. The future of ADC therapy in bladder cancer is bright, with immense potential to revolutionize the standard of care and improve patient outcomes globally.
抗体药物偶联物（ADCs）已成为肿瘤学中一种变革性的治疗方式，在靶向肿瘤细胞的同时保护健康组织，实现了前所未有的精准度。在膀胱癌这种复发率高且治疗选择有限的恶性肿瘤中，ADCs通过靶向特定的肿瘤相关抗原，如NECTIN-4和人表皮生长因子受体2（HER2），已显示出显著疗效。本综述全面评估了基于ADCs的膀胱癌治疗的当前状况，重点关注其作用机制、临床疗效和安全性。
我们系统分析了2004年至2025年的232项临床试验，发现ADCs研究呈显著上升趋势，特别是在2019年美国食品药品监督管理局（FDA）加速批准恩杂鲁胺后。
我们的研究结果突出了HER2、NECTIN4和PD-1作为研究最广泛的分子靶点的主导地位，同时将ADCs与免疫检查点抑制剂联合使用的兴趣也日益增加。在地理上，美国和中国在ADCs临床试验方面领先，这反映了强大的研究投入和基础设施。
尽管取得了有前景的进展，但毒性管理、患者分层和试验设计等挑战仍然至关重要。本综述强调了在ADCs技术方面持续创新和采用个性化方法克服这些限制的重要性，最终为膀胱癌患者开辟更有效、更安全的治疗选择之路。膀胱癌ADCs治疗的未来前景光明，具有彻底改变护理标准并改善全球患者预后的巨大潜力。
