Nectin-4 expression patterns and therapeutics in oncology

Cancer Lett. 2025 Jul 10:622:217681. doi: 10.1016/j.canlet.2025.217681. Epub 2025 Apr 8.

Abstract

Nectin-4 is a transmembrane receptor that is implicated in migration, adhesion, and proliferation of tumor cells. It has minimal expression in healthy adult tissue but is overexpressed in a number of cancers, with higher expression levels seen in breast, bladder, colorectal, gallbladder, gastric, and non-small cell lung cancers. Enfortumab vedotin is an antibody-drug conjugate against nectin-4 that has been studied in a number of solid tumors and is FDA-approved for advanced urothelial cancers (including in combination with pembrolizumab). There are a number of other nectin-4-targeting agents under investigation. This review summarizes nectin-4 expression (membranous and cytoplasmic)/amplification in cancer and its potential as a response biomarker, as well as clinical trials of enfortumab vedotin and novel nectin-4 targeting agents. Biomarker-driven approaches merit investigation for nectin-4 directed across tumor types.

Keywords: Antibody-drug conjugate; Biomarker-driven approach; Enfortumab vedotin; Nectin-4.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Cell Adhesion Molecules* / antagonists & inhibitors
  • Cell Adhesion Molecules* / genetics
  • Cell Adhesion Molecules* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nectins
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neoplasms* / pathology

Substances

  • NECTIN4 protein, human
  • Cell Adhesion Molecules
  • Biomarkers, Tumor
  • enfortumab vedotin
  • Antibodies, Monoclonal
  • Nectins