Cysteine cathepsin (CTS)

Cysteine cathepsins are a family of lysosomal enzymes, including cathepsins B, L, and S, that are frequently overexpressed and highly active in the microenvironment of various solid tumors (Source: Olson and Joyce, 2015, Nature Reviews Cancer). While they primarily function in intracellular protein turnover within lysosomes, their secretion into the extracellular space facilitates the degradation of the extracellular matrix, thereby promoting tumor invasion, angiogenesis, and metastasis (Source: Rawat et al., 2021, Frontiers in Oncology). The 'active' form of these enzymes is a specific focus for drug development, as it distinguishes functional proteases from their inactive zymogen precursors. Therapeutic strategies include the use of small molecule inhibitors to block tumor progression and the development of activity-based probes, such as V002, for real-time surgical imaging of tumor margins (Source: Vergent Bioscience, 2024). Additionally, the localized activity of these cathepsins is exploited in the design of antibody-drug conjugates and prodrugs that release their cytotoxic payload only upon cleavage by the enzyme within the tumor site (Source: Gondi and Rao, 2013, Expert Opinion on Therapeutic Targets). Despite their potential, drug development has faced challenges regarding selectivity and off-target effects in normal tissues where these enzymes maintain basal physiological functions.

Other names

Lysosomal cysteine proteaseCysteine-type endopeptidasePapain-like proteaseCysteine protease

Inhibition of proteolytic activity to prevent extracellular matrix degradation and tumor invasion; or activation of activity-based probes and prodrugs specifically within the acidic tumor microenvironment.