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Nectin-4 and Trop-2 expression in collecting duct carcinoma: new promising therapeutic targets

A Rametta1, M Stellato1, S Rota1

  • 1Department of Genitourinary Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

ESMO Open
|July 29, 2026
PubMed
Abstract

Insights

Nectin-4 and Trop-2 are frequently expressed in collecting duct carcinoma (CDC), suggesting a potential for targeted therapies. These findings support further investigation of antibody-drug conjugates (ADCs) for this rare cancer.

Area of Science:

  • Oncology
  • Pathology
  • Translational Research

Background:

  • Collecting duct carcinoma (CDC) is a rare, aggressive kidney cancer with limited treatment options.
  • CDC shares morphologic and embryologic similarities with urothelial carcinoma.
  • Biomarker-driven strategies are lacking for CDC.

Purpose of the Study:

  • To investigate the expression of Nectin-4 and Trop-2 in CDC.
  • To evaluate the potential of Nectin-4 and Trop-2 as therapeutic targets in CDC.
  • To explore the biological overlap between CDC and urothelial carcinoma.

Main Methods:

  • Retrospective analysis of 59 CDC tumor samples from the CICERONE study.
  • Central pathological review by expert genitourinary pathologists.
  • Immunohistochemical analysis for Nectin-4 and Trop-2 expression.

Main Results:

  • Nectin-4 was expressed in 41% of CDC cases.
  • Trop-2 was expressed in 89% of CDC cases, often with strong and diffuse staining.
  • No significant associations between marker expression and clinicopathologic features were identified.

Conclusions:

  • Nectin-4 and Trop-2 are frequently expressed in CDC, supporting a biological link to urothelial carcinoma.
  • These findings provide a rationale for evaluating antibody-drug conjugate (ADC) strategies in CDC.
  • Ongoing clinical trials are investigating ADC-based combinations for rare malignancies like CDC.
Keywords:
Nectin-4Trop-2collecting duct carcinomaenfortumab vedotinrenal carcinoma

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