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HER2 in urothelial cancer: clinical speed outpacing diagnostic clarity

Nature Reviews Urology (2026) Cite this article

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HER2-targeted antibody–drug conjugates are rapidly transforming the treatment landscape of urothelial carcinoma, with recent clinical trials positioning HER2-directed therapy as a new therapeutic pillar. Yet, this therapeutic acceleration has exposed a fundamental challenge: HER2-targeted drugs are advancing swiftly into early disease settings, but the field still lacks a coherent definition of what ‘HER2-positive’ means in urothelial cancer.

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Fig. 1: Comparative HER2 immunohistochemistry scoring frameworks in breast and gastro-oesophageal junction cancers.
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Authors and Affiliations

  1. Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Emanuele Crupi

  2. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA

    Filippo Pederzoli

  3. Genitourinary Oncology, The Royal Marsden Hospital NHS Foundation Trust, London, UK

    Robert A. Huddart & Daniele Raggi

  4. The Institute of Cancer Research (ICR), London, UK

    Robert A. Huddart

  5. Department of Pathology and Laboratory Medicine, Brown University Warren Alpert Medical School, the Legorreta Cancer Center at Brown University and Brown University Health, Providence, RI, USA

    Cheng Liang

  6. Department of Surgery (Urology), Brown University Warren Alpert Medical School, the Legorreta Cancer Center at Brown University and Brown University Health, Providence, RI, USA

    Cheng Liang

Authors
  1. Emanuele Crupi
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  2. Filippo Pederzoli
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  4. Cheng Liang
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  5. Daniele Raggi
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Correspondence to Emanuele Crupi or Daniele Raggi.

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The authors declare no competing interests.

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Crupi, E., Pederzoli, F., Huddart, R.A. et al. HER2 in urothelial cancer: clinical speed outpacing diagnostic clarity. Nat Rev Urol (2026). https://doi.org/10.1038/s41585-026-01151-w

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