An update on antibody–drug conjugates in urothelial carcinoma: state of the art strategies and what comes next

Alberto D'Angelo, Robert Chapman, Marianna Sirico, Navid Sobhani, Martina Catalano, Enrico Mini, Giandomenico Roviello

Research output: Contribution to journalReview articlepeer-review

1 Citation (SciVal)

Abstract

In recent years, considerable progress has been made in increasing the knowledge of tumour biology and drug resistance mechanisms in urothelial cancer. Therapeutic strategies have significantly advanced with the introduction of novel approaches such as immune checkpoint inhibitors and Fibroblast Growth Factor Receptor inhibitors. However, despite these novel agents, advanced urothelial cancer is often still progressive in spite of treatment and correlates with a poor prognosis. The introduction of antibody-drug conjugates consisting of a target-specific monoclonal antibody covalently linked to a payload (cytotoxic agent) is a novel and promising therapeutic strategy. In December 2019, the US Food and Drug Administration (FDA) granted accelerated approval to the nectin-4-targeting antibody-drug conjugate, enfortumab vedotin, for the treatment of advanced or metastatic urothelial carcinomas that are refractory to both immune checkpoint inhibitors and platinum-based treatment. Heavily pre-treated urothelial cancer patients reported a significant, 40% response to enfortumab vedotin while other antibody-drug conjugates are currently still under investigation in several clinical trials. We have comprehensively reviewed the available treatment strategies for advanced urothelial carcinoma and outlined the mechanism of action of antibody-drug conjugate agents, their clinical applications, resistance mechanisms and future strategies for urothelial cancer.

Original languageEnglish
Pages (from-to)191-205
Number of pages15
JournalCancer Chemotherapy and Pharmacology
Volume90
Issue number3
Early online date11 Aug 2022
DOIs
Publication statusPublished - 30 Sept 2022

Keywords

  • Antibody–drug conjugate
  • Bladder
  • Enfortumab vedotin
  • HER2
  • Immunotherapy
  • Nectin-4
  • Sacituzumab govitecan
  • Urothelial cancer

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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