Antibody-drug conjugates (ADCs) have been a significant advancement in cancer therapy, particularly for urothelial cancer (UC). These innovative treatments, originally developed for hematological malignancies, use target-specific monoclonal antibodies linked to potent cytotoxic agents. This rational drug design efficiently delivers cancer cell-killing agents to cells expressing specific surface proteins, which are abundant in UC owing to their high antigen expression. UC is an ideal candidate for ADC therapy, as it enhances on-target efficacy while mitigating systemic toxicity. In recent years, considerable progress has been made in understanding the biology and mechanisms of tumor progression in UC. However, despite the introduction of immune checkpoint inhibitors, advanced UC is characterized by rapid progression and poor survival rates. Targeted therapies that have been developed include the anti-nectin 4 ADC enfortumab vedotin and the fibroblast growth factor receptor inhibitor erdafitinib. Enfortumab vedotin has shown efficacy in prospective studies in patients with advanced UC, alone and in combination with pembrolizumab. The anti-Trop-2 ADC sacituzumab govitecan has also demonstrated effectiveness in single-armed studies. This review highlights the mechanism of action of ADCs, their application in mono- and combination therapies, primary mechanisms of resistance, and future perspectives for their clinical use in UC treatment. ADCs have proven to be an increasingly vital component of the therapeutic landscape for urothelial carcinoma, filling a gap in the treatment of this progressive disease.
抗体药物偶联物（ADC）是癌症治疗领域的重要进展，尤其对尿路上皮癌（UC）具有显著意义。这类创新疗法最初为血液系统恶性肿瘤开发，通过靶向特异性单克隆抗体与高效细胞毒性药物结合，利用理性药物设计将癌细胞杀伤剂精准递送至表达特定表面蛋白的细胞。由于UC细胞表面抗原高表达，使其成为ADC治疗的理想靶点，在增强靶向疗效的同时有效降低全身毒性。近年来，对UC肿瘤生物学特性及进展机制的理解已取得长足进步，但尽管免疫检查点抑制剂已投入临床，晚期UC仍以快速进展和低生存率为特征。目前已开发的靶向治疗包括靶向Nectin-4的ADC药物enfortumab vedotin，以及成纤维细胞生长因子受体抑制剂erdafitinib。前瞻性研究显示enfortumab vedotin单药或联合帕博利珠单抗在晚期UC患者中均展现疗效，而靶向Trop-2的ADC药物sacituzumab govitecan在单臂研究中也显示出治疗潜力。本综述重点阐述ADC的作用机制、在单药及联合疗法中的应用、主要耐药机制，以及其在UC治疗中的临床应用前景。ADC已成为尿路上皮癌治疗体系中日益重要的组成部分，为这一进展性疾病的治疗填补了关键空白。
Antibody-Drug Conjugates in Urothelial Cancer: From Scientific Rationale to Clinical Development
肿瘤(癌症)患者之家