Page 12 - GPD-4-3

Gene & Protein in Disease

REVIEW ARTICLE
Cathepsin proteases and cancer progression: A

niche for dual-acting anticancer therapeutics

1,2
Surinder M. Soond *
1 Division of International Exchanges, Faculty of Education, Northeastern Agricultural University,
Harbin, Heilongjiang, China
2 Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russian
Federation

Abstract
Cathepsin proteases have captivated the scientific community for many years
owing to their deregulated expression, activation status, and potential role in the
proliferation and progression of specific cancer types. These efforts have led to the
development of several therapeutic strategies targeting specific cathepsin proteases.
This development has been further driven by the identification of important
cathepsin protease-specific target proteins. Despite the limitations of these
approaches, primarily due to the lack of known specificity of cathepsin proteases in
targeting substrate proteins, an alternative strategy may involve the identification
and development of dual-acting therapeutics. We propose that these dual-acting
therapeutics can selectively interfere with the protein constituents involved in
forming a cathepsin-targeted protein complex while simultaneously inhibiting
*Corresponding author:
Surinder M. Soond the cognate cathepsin protease. Considering this novel paradigm, we evaluated
(s.soond@neau.edu.cn) the potential of dual-acting therapeutics against other well-documented mimetic
Citation: Soond SM. Cathepsin therapeutics designed to target intermediates in the apoptosis pathway. Some of
proteases and cancer progression: these therapeutics may represent promising candidates for further testing as dual-
A niche for dual-acting anticancer acting anticancer therapeutics, either alone or in combination regimens.
therapeutics. Gene Protein Dis.
2025;4(3):4768.
doi: 10.36922/gpd.4768
Keywords: Cathepsins; Apoptosis; Cancer; Metastasis; BH proteins; Dual-acting
Received: September 4, 2024 therapeutics
Revised: October 25, 2024
Accepted: October 29, 2024
Published online: November 27, 1. Introduction
2024
Discerning the activation of cathepsin proteases (Cts) and the protein substrates they
Copyright: © 2024 Author(s). target in molecular cell biology has had far-reaching effects over the past 20 years. As a
This is an Open-Access article
distributed under the terms of the group of proteases central to intracellular lysosomal function, Cts have recently gained
Creative Commons Attribution importance in extracellular matrix (ECM) remodeling. Considering their emerging
License, permitting distribution, and differential subcellular localization, functions, and biological effects derived
and reproduction in any medium,
provided the original work is therefrom, Cts collectively highlight their suitability for therapeutic targeting in a
properly cited. number of diseases, including cancer. The Cts family of lysosomal proteases comprises
1,2
Publisher’s Note: AccScience 16 proteins, classified into cysteine, aspartic, and serine proteases, namely, Cts B, C, F,
Publishing remains neutral with H, K, L, O, S, V, Z/X, and W; Cts D or E; and Cts A or G, respectively. Furthermore,
regard to jurisdictional claims in
published maps and institutional selective cysteine proteases such as Cts (B, H, Z/X, or C) reportedly possess exopeptidase
3,4
affiliations. or endopeptidase activities (as observed in Cts B, S, K, V, F, and L). However, upon

Volume 4 Issue 3 (2025) 1 doi: 10.36922/gpd.4768