D’Angelo A, Catalano M, De Gennaro Aquino I, Gangi V, Roviello G. Antibody-drug conjugates in metastatic urothelial cancer: Highway to heaven. World J Clin Oncol 2025; 16(9): 106646 [PMID: 41024847 DOI: 10.5306/wjco.v16.i9.106646]
Corresponding Author of This Article
Giandomenico Roviello, MD, PhD, Associate Professor, School of Health Sciences, University of Florence, via lePieraccini 6, Florence 50139, Italy. giandomenico.roviello@unifi.it
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Sep 24, 2025; 16(9): 106646 Published online Sep 24, 2025. doi: 10.5306/wjco.v16.i9.106646
Antibody-drug conjugates in metastatic urothelial cancer: Highway to heaven
Alberto D’Angelo, Martina Catalano, Irene De Gennaro Aquino, Valeria Gangi, Giandomenico Roviello
Alberto D’Angelo, Department of Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S57A7, United Kingdom
Martina Catalano, Giandomenico Roviello, Department of Health Sciences, Section of Clinical Pharmacology Oncology, University of Florence, Florence 50134, Italy
Irene De Gennaro Aquino, Valeria Gangi, School of Human Health Sciences, University of Florence, Florence 50134, Tuscany, Italy
Co-first authors: Alberto D’Angelo and Martina Catalano.
Author contributions: D’Angelo A and Catalano M contributed to conceptualization, data curation, and writing of the original draft; Roviello G contributed to methodology, visualization, and validation; De Gennaro Aquino I and Gangi V contributed to resources.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Giandomenico Roviello, MD, PhD, Associate Professor, School of Health Sciences, University of Florence, via lePieraccini 6, Florence 50139, Italy. giandomenico.roviello@unifi.it
Received: March 4, 2025 Revised: April 15, 2025 Accepted: August 12, 2025 Published online: September 24, 2025 Processing time: 203 Days and 22.8 Hours
Abstract
Metastatic urothelial carcinoma (mUC) is a challenging malignancy with historically limited treatment options. Advances in understanding its biology have enabled the development of innovative therapies, including immune checkpoint inhibitors and antibody-drug conjugates (ADCs). ADCs, such as enfortumab vedotin, sacituzumab govitecan, and trastuzumab deruxtecan, represent transformative advancements, offering targeted delivery of cytotoxic agents. This review highlights the evolving role of ADCs in mUC, examining their mechanisms, clinical efficacy, patient selection criteria, genetic insights, and future directions in personalized treatment strategies.
Core Tip: Metastatic urothelial carcinoma (mUC) remains a challenging malignancy with poor prognosis despite advances in treatment. Platinum-based chemotherapy has been the standard, but its toxicity limits its use in many patients. Immune checkpoint inhibitors have improved survival, yet most patients eventually progress. Antibody-drug conjugates (ADCs) represent a transformative approach, delivering cytotoxic agents directly to tumor cells while minimizing systemic toxicity. Enfortumab vedotin and sacituzumab govitecan have shown significant efficacy, even in heavily pretreated patients. Ongoing research aims to optimize ADC combinations and identify biomarkers for patient selection, paving the way for more personalized and effective mUC therapies.
