Shih Chia-Hsien, Lin Yu-Hua, Luo Hao-Lun, Sung Wen-Wei
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan.
Front Pharmacol. 2024 Mar 20;15:1326296. doi: 10.3389/fphar.2024.1326296. eCollection 2024.
Urothelial carcinoma (UC) is a common cancer characterized by high morbidity and mortality rates. Despite advancements in treatment, challenges such as recurrence and low response rates persist. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach for various cancers, although their application in UC is currently limited. This review focuses on recent research regarding ADCs designed to treat UC by targeting human epidermal growth factor receptor 2 (HER2), a surface antigen expressed on tumor cells. ADCs comprise three main components: an antibody, a linker, and a cytotoxic payload. The antibody selectively binds to tumor cell surface antigens, facilitating targeted delivery of the cytotoxic drug, while linkers play a crucial role in ensuring stability and controlled release of the payload. Cleavable linkers release the drug within tumor cells, while non-cleavable linkers ensure stability during circulation. The cytotoxic payload exerts its antitumor effect by disrupting cellular pathways. HER2 is commonly overexpressed in UCs, making it a potential therapeutic target. Several ADCs targeting HER2 have been approved for cancer treatment, but their use in UC is still being tested. Numerous HER2 ADCs have demonstrated significant growth inhibition and induction of apoptosis in translational models of HER2-overexpressing bladder cancer. Ongoing clinical trials are assessing the efficacy and safety of ADCs targeting HER2 in UC, with the aim of determining tumor response and the potential of ADCs as a treatment option for UC patients. The development of effective therapies with improved response rates and long-term effectiveness is crucial for advanced and metastatic UC. ADCs targeting HER2 show promise in this regard and merit further investigation for UC treatment.
尿路上皮癌（UC）是一种常见癌症，其发病率和死亡率都很高。尽管治疗方面取得了进展，但复发和低反应率等挑战依然存在。抗体药物偶联物（ADC）已成为治疗多种癌症的一种有前景的治疗方法，不过其在UC中的应用目前还很有限。本综述聚焦于近期有关旨在通过靶向人表皮生长因子受体2（HER2，一种在肿瘤细胞上表达的表面抗原）来治疗UC的ADC的研究。ADC由三个主要成分组成：抗体、连接子和细胞毒性载荷。抗体选择性地结合肿瘤细胞表面抗原，促进细胞毒性药物的靶向递送，而连接子在确保载荷的稳定性和控释方面起着关键作用。可裂解连接子在肿瘤细胞内释放药物，而非可裂解连接子则确保在循环过程中的稳定性。细胞毒性载荷通过破坏细胞途径发挥其抗肿瘤作用。HER2在UC中通常过表达，使其成为一个潜在的治疗靶点。几种靶向HER2的ADC已被批准用于癌症治疗，但其在UC中的应用仍在试验中。许多HER2 ADC在HER2过表达膀胱癌的转化模型中已显示出显著的生长抑制和凋亡诱导作用。正在进行的临床试验正在评估靶向HER2的ADC在UC中的疗效和安全性，目的是确定肿瘤反应以及ADC作为UC患者治疗选择的潜力。开发有效疗法，提高反应率和长期有效性，对于晚期和转移性UC至关重要。靶向HER2的ADC在这方面显示出前景，值得进一步研究用于UC治疗。
