PDF(Pubmed)
Abstract：
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.
摘要：
抗体-药物偶联物(ADC)在癌症治疗中取得了重大进展,特别是尿路上皮癌（UC）。这些创新的治疗方法，最初是为血液恶性肿瘤开发的，使用与有效细胞毒性剂连接的靶特异性单克隆抗体。这种合理的药物设计有效地将癌细胞杀伤剂提供给表达特定表面蛋白的细胞，由于其高抗原表达，在UC中含量丰富。UC是ADC治疗的理想候选者，因为它增强了目标疗效，同时减轻了全身毒性。近年来,在了解UC的生物学和肿瘤进展机制方面已经取得了相当大的进展。然而,尽管引入了免疫检查点抑制剂，晚期UC的特点是进展迅速，生存率低。已经开发的靶向治疗包括抗-nectin4ADCenfortumabvedotin和成纤维细胞生长因子受体抑制剂erdafitinib。Enfortumabvedotin已在晚期UC患者的前瞻性研究中显示出疗效，单独和与pembrolizumab联合使用。抗Trop-2ADCsacituzumabgovitecan在单臂研究中也证明了有效性。这篇综述强调了ADC的作用机制，它们在单一疗法和联合疗法中的应用，抗性的主要机制，以及它们在UC治疗中的临床应用前景。ADC已被证明是尿路上皮癌治疗景观中越来越重要的组成部分，填补了治疗这种进行性疾病的空白。
