Cysteine cathepsin proteases as pharmacological targets in cancer.
Proteolytic activity is required for several key pro-tumorigenic processes: angiogenesis, invasion and metastasis. Consequently, increases in protease expression and activity are frequently reported in human cancers, and correlate with malignant progression and poor patient prognosis. Cysteine cathepsin proteases have recently emerged as an important class of proteolytic enzymes in cancer development, and cysteine cathepsin inhibitors have been proposed as anticancer agents. In this review, we highlight recent studies that now allow us to evaluate critically whether cysteine cathepsin inhibition represents a viable therapeutic strategy for the treatment of cancer.
Palermo
Carmela
C
Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 372, New York, NY 10021, USA.
Joyce
Johanna A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002403:Cathepsins / Q000378:metabolism*; D002986:Clinical Trials as Topic; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D002403:Cathepsins