Cysteine cathepsins as therapeutic targets in inflammatory diseases

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

Article Highlights

• Cysteine cathepsins play a role in the development and progression of inflammation-associated diseases.

• Inhibition or genetic silencing of cysteine cathepsins ameliorate syndromes in several diseases.

• Cysteine cathepsins overexpression in diseased tissue can be used beyond direct inhibition for both diagnostic and treatment purposes.

• The application of cysteine cathepsin inhibitors faces many challenges mainly due to off- and on-target side effects.

• Research is expanding towards diagnostic imaging of cysteine cathepsins using different imaging modalities, including fluorescence (image-guided surgery), CT, PET and MRI.

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Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Declaration of Interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

The work of the authors was supported by the research grants from Slovene Research Agency [P1-0140, N1-0127 and J1-1710] and ICGEB (CRP/SVN 16-01) to B.T.