Nectin-4: a Tumor Cell Target and Status of Inhibitor Development

Curr Oncol Rep. 2023 Mar;25(3):181-188. doi: 10.1007/s11912-023-01360-1. Epub 2023 Jan 25.

Abstract

Purpose of review: This study aims to gather the current state of the literature about anti-Nectin-4 innovative associations in solid tumors and to investigate underlying resistance mechanisms.

Recent findings: Antibody-drug conjugate (ADC) targeting Nectin-4 efficacy gained attention and offers a promising association with other antineoplastic drugs especially in urothelial carcinoma. The heterogeneity of Nectin-4 expression across the molecular subtypes was highlighted especially in urothelial cancers. A unique study using preclinical models demonstrated an upregulation of P-gp expression, which may explain the anti-Nectin-4 resistance mechanisms. Further studies are urgently needed to understand anti-Nectin-4 sensitivity and resistance phenomenon. The growing therapeutic associations of enfortumab vedotin offer optimistic opportunities in management and treatment of wide range of solid tumors including rare aggressive malignancies.

Keywords: Antidrug conjugate; Biomarker; Heterogeneity; Malignancies; Nectin-4; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Transitional Cell* / drug therapy
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / therapeutic use
  • Humans
  • Immunoconjugates* / therapeutic use
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Cell Adhesion Molecules
  • Antineoplastic Agents
  • Immunoconjugates