Ismaili N. Emergence of human epidermal growth factor receptor 2 as a key biomarker and therapeutic target in advanced urothelial carcinoma. World J Clin Oncol 2026; 17(7): 116520 [DOI: 10.5306/wjco.116520]
Corresponding Author of This Article
Nabil Ismaili, MD, Associate Professor, Chief Physician, Director, Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS), Mohammed VI Foundation of Sciences and Health (FM6SS), Boulevard Mohamed Taïeb Naciri, Commune Hay Hassani, Casablanca 82403, Morocco. ismailinabil@yahoo.fr
Research Domain of This Article
Oncology
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editorial
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Ismaili N. Emergence of human epidermal growth factor receptor 2 as a key biomarker and therapeutic target in advanced urothelial carcinoma. World J Clin Oncol 2026; 17(7): 116520 [DOI: 10.5306/wjco.116520]
World J Clin Oncol. Jul 24, 2026; 17(7): 116520 Published online Jul 24, 2026. doi: 10.5306/wjco.116520
Emergence of human epidermal growth factor receptor 2 as a key biomarker and therapeutic target in advanced urothelial carcinoma
Nabil Ismaili
Nabil Ismaili, Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS), Mohammed VI Foundation of Sciences and Health (FM6SS), Casablanca 82403, Morocco
Author contributions: Ismaili N was responsible for conceptualization, methodology and software, validation, formal analysis and investigation, resources, data curation, writing original draft, review, and editing and visualization.
AI contribution statement: I used ChatGPT and Grammarly for language polishing, grammar correction, and occasional rephrasing of sentences to improve readability and fluency.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Nabil Ismaili, MD, Associate Professor, Chief Physician, Director, Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS), Mohammed VI Foundation of Sciences and Health (FM6SS), Boulevard Mohamed Taïeb Naciri, Commune Hay Hassani, Casablanca 82403, Morocco. ismailinabil@yahoo.fr
Received: November 13, 2025 Revised: November 21, 2025 Accepted: December 23, 2025 Published online: July 24, 2026 Processing time: 253 Days and 6.3 Hours
Abstract
Urothelial carcinoma (UC) represents a significant global health challenge, particularly in its advanced stages where treatment options remain limited and outcomes poor. While platinum-based chemotherapy has historically formed the backbone of first-line treatment for metastatic disease, the median overall survival rarely exceeds 15 months, highlighting the urgent need for more effective therapeutic strategies. The recent molecular characterization of UC has revealed human epidermal growth factor receptor 2 (HER2) as a frequently altered pathway, especially in upper tract UC, where it demonstrates a strong association with high-grade disease and aggressive behavior. The emergence of antibody-drug conjugates targeting HER2 has revolutionized the treatment landscape, offering new hope for patients with HER2-expressing tumors. This comprehensive review contextualizes the recent findings of Huang and He, who published a study in World Journal of Clinical Oncology on HER2 overexpression in upper tract UC within the evolving therapeutic paradigm, emphasizing the critical importance of integrating biomarker-driven strategies, particularly anti-HER2 antibody-drug conjugates in combination with immunotherapy, into the management algorithm of advanced UC. We synthesize evidence from multiple recent studies and clinical trials to provide a thorough overview of the current status and future directions of HER2-targeted therapy in UC.
Core Tip: This commentary highlights the critical findings published in the World Journal of Clinical Oncology by Huang and He, which establish a strong link between human epidermal growth factor receptor 2 (HER2) overexpression and high-grade upper tract urothelial carcinoma (UC), revealing a distinct biological profile compared to bladder cancer. These results gain immediate clinical relevance with the recent paradigm-shifting data from the phase 3 RC48-C016 trial. The combination of the anti-HER2 antibody-drug conjugate disitamab vedotin and the anti-programmed cell death protein-1 toripalimab has demonstrated superior efficacy over standard chemotherapy in first-line HER2-expressing metastatic UC, nearly doubling progression-free survival and significantly improving overall survival with a better safety profile. Given that nearly half of upper tract UC tumors are HER2-positive, these findings urgently position a substantial patient subset as potential candidates for this novel, biomarker-driven therapy, heralding a new era in UC treatment.
