Cysteine cathepsins as therapeutic targets in inflammatory diseases

Expert Opin Ther Targets. 2020 Jun;24(6):573-588. doi: 10.1080/14728222.2020.1746765. Epub 2020 Apr 6.

Abstract

Introduction: Cysteine cathepsins are involved in the development and progression of numerous inflammation-associated diseases such as cancer, arthritis, bone and immune disorders. Consequently, there is a drive to progress research efforts focused on cathepsin use in diagnostics and as therapeutic targets in disease.Areas covered: This review discusses the potential of cysteine cathepsins as therapeutic targets in inflammation-associated diseases and recent advances in preclinical and clinical research. We describe direct targeting of cathepsins for treatment purposes and their indirect use in diagnostics.Expert opinion: The targeting of cysteine cathepsins has not translated into the clinic; this failure is attributed to off- and on-target side effects and/or the lack of companion biomarkers. This field now embraces developments in diagnostic imaging, the activation of prodrugs and antibody-drug conjugates for targeted drug delivery. The future lies in improved molecular tools and therapeutic concepts that will find a wide spectrum of uses in diagnostic and therapeutic applications.

Keywords: Biomarkers; cysteine cathepsins; diagnostics; inflammation-associated diseases; inhibition; theranostics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cathepsins / metabolism*
  • Cysteine / metabolism
  • Diagnostic Imaging / methods
  • Drug Delivery Systems
  • Humans
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / pharmacology
  • Inflammation / diagnosis
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Molecular Targeted Therapy*
  • Prodrugs

Substances

  • Immunoconjugates
  • Prodrugs
  • Cathepsins
  • Cysteine