NECTIN4

Overview

NECTIN4 (nectin cell adhesion molecule 4, formerly PVRL4) encodes a cell-adhesion molecule of the nectin family. It is highly expressed on urothelial carcinoma cells and is the target of enfortumab vedotin (EV), an antibody-drug conjugate approved for bladder cancer. Focal amplification of the NECTIN4 locus has been identified as one of the most frequent focal copy-number gains in muscle-invasive bladder cancer.

Alterations observed in the corpus

  • Focal amplification (PVRL4/NECTIN4) in 19% of muscle-invasive bladder carcinomas, the highest frequency focal amplification in the TCGA bladder cohort; a potential therapeutic target PMID:24476821
  • PVRL4 (NECTIN4) amplification was identified by GISTIC analysis as a recurrent focal amplification in muscle-invasive bladder cancer (MIBC), consistent with prior TCGA findings PMID:28988769

Cancer types (linked)

  • BLCA (Bladder Urothelial Carcinoma): Focal amplification at 19% frequency in muscle-invasive disease; NECTIN4 is a validated therapeutic target in this cancer type PMID:24476821

Co-occurrence and mutual exclusivity

  • Amplification co-occurs with other focal amplification events in bladder cancer, including PPARG and E2F3 amplifications PMID:24476821

Therapeutic relevance

  • NECTIN4 is targeted by enfortumab vedotin (EV), an antibody-drug conjugate with FDA approval in locally advanced or metastatic urothelial carcinoma; amplification may predict increased NECTIN4 expression and sensitivity.

Open questions

  • Whether NECTIN4 amplification correlates with NECTIN4 protein expression and EV response remains to be formally established in large cohorts.

Sources

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