Antibody-Drug Conjugates in Non-Small Cell Lung Cancer: State of the Art and Future Perspectives

Carol Zanchetta, Lorenzo De Marchi, Marianna Macerelli, Giacomo Pelizzari, Jacopo Costa, Giuseppe Aprile, Francesco Cortiula*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

Antibody–drug conjugates (ADCs) represent one of the most promising and rapidly emerging anti-cancer therapies because they combine the cytotoxic effect of the conjugate payload and the high selectivity of the monoclonal antibody, which binds a specific membrane antigen expressed by the tumor cells. In non-small cell lung cancer (NSCLC), ADCs are being investigated targeting human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), trophoblast cell surface antigen 2 (TROP2), Mesenchymal–epithelial transition factor (c-MET), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5). To date, Trastuzumab deruxtecan is the only ADC that has been approved by the FDA for the treatment of patients with NSCLC, but several ongoing studies, both using ADCs as monotherapy and combined with other therapies, are investigating the efficacy of new ADCs. In this review, we describe the structures and mechanism of action of different ADCs; we present the evidence derived from the main clinical trials investigating ADCs’ efficacy, focusing also on related toxicity; and, finally, we discuss future perspectives in terms of toxicity management, possible biomarkers, and the identification of resistance mechanisms.

Original languageEnglish
Article number221
JournalInternational Journal of Molecular Sciences
Volume26
Issue number1
DOIs
Publication statusPublished - Jan 2025

Keywords

  • ADC
  • NSCLC
  • Trastuzumab deruxtecan
  • target therapy
  • Humans
  • Immunoconjugates/therapeutic use
  • Carcinoma, Non-Small-Cell Lung/drug therapy metabolism
  • Lung Neoplasms/drug therapy metabolism
  • Animals

Fingerprint

Dive into the research topics of 'Antibody-Drug Conjugates in Non-Small Cell Lung Cancer: State of the Art and Future Perspectives'. Together they form a unique fingerprint.

Cite this