Proteases as activators for cytotoxic prodrugs in antitumor therapy.
Proteases are often overexpressed in tumor cells and/or the stromal compartment and can thus be exploited in tumor therapy to activate cytotoxic prodrugs as, for example, in cytolytic fusion proteins, and for tumor imaging. Specifically, we discuss cathepsin B-activated prodrug conjugates, antibody-directed prodrug therapy, protease-activated peptide-thapsigargin conjugates, protease-activated cytotoxic receptor ligands and other cytotoxic proteins, protease-mediated activation of anthrax toxin, granzyme B as a therapeutic principle in cytolytic fusion proteins, and tumor-imaging based on deregulated proteases.
Roche Pharma Research and Early Development (pRED), Roche Diagnostics GmbH, Im Nonnenwald 2, D 82372 Penzberg, Germany. ulrich.weidle@roche.com.
Ulrich H
UH
Weidle
Georg
G
Tiefenthaler
Guy
G
Georges
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D002401:Cathepsin B / Q000502:physiology; D053804:Granzymes / Q000502:physiology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000378:metabolism* / Q000627:therapeutic use; D059748:Proteolysis; D012697:Serine Endopeptidases / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
D000970:Antineoplastic Agents; D011355:Prodrugs; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C485596:ST14 protein, human; D014568:Urokinase-Type Plasminogen Activator; C533912:CTSB protein, human; D002401:Cathepsin B; D020782:Matrix Metalloproteinases
Anthrax toxin; Antibody-drug conjugates; antibody-directed enzyme prodrug therapy; cytotoxic receptor ligand(s); granzyme B; probody; review; thapsigargin