Tumor-associated cathepsins and matrix metalloproteases

Tumor-associated cathepsins and matrix metalloproteases (MMPs) represent a broad class of proteolytic enzymes that are significantly upregulated within the tumor microenvironment (Sevenich & Joyce, 2014, Nature Reviews Cancer). Cathepsins, primarily cysteine proteases like Cathepsin B and L, and MMPs, such as MMP-2 and MMP-9, are essential for the degradation of the extracellular matrix, which facilitates tumor cell invasion, migration, and metastasis (Jabłońska-Trypuć et al., 2016, Journal of Enzyme Inhibition and Medicinal Chemistry). Beyond structural remodeling, these enzymes also modulate the activity of various growth factors and cytokines, promoting angiogenesis and immune evasion (Olson & Joyce, 2015, Nature Reviews Cancer). While early clinical trials with broad-spectrum MMP inhibitors failed due to dose-limiting toxicities like musculoskeletal syndrome, these proteases remain high-interest targets for modern precision medicine (Gondi & Rao, 2013, Cancer and Metastasis Reviews). Current strategies often utilize the high local concentration of these enzymes to activate 'masked' therapeutics, such as protease-cleavable antibody-drug conjugates or prodrugs, thereby concentrating the drug's effect within the tumor while sparing healthy tissues.

Other names

Tumor-associated proteasesCancer-associated proteasesTAPsPericellular proteases

Direct inhibition of catalytic activity to prevent matrix degradation; Proteolytic cleavage of peptide linkers in prodrugs or Probody drug conjugates to release active cytotoxic payloads specifically within the tumor microenvironment.