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Nat Rev Cancer. 2015 Dec;15(12):712-29. doi: 10.1038/nrc4027.

Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response.

Olson OC1,2, Joyce JA1,3,4.

Author information

1
Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center.
2
Gerstner Sloan Kettering Graduate School of Biomedical Science, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
3
Department of Oncology, University of Lausanne.
4
Ludwig Institute for Cancer Research, University of Lausanne, CH-1066 Lausanne, Switzerland.

Abstract

Cysteine cathepsin protease activity is frequently dysregulated in the context of neoplastic transformation. Increased activity and aberrant localization of proteases within the tumour microenvironment have a potent role in driving cancer progression, proliferation, invasion and metastasis. Recent studies have also uncovered functions for cathepsins in the suppression of the response to therapeutic intervention in various malignancies. However, cathepsins can be either tumour promoting or tumour suppressive depending on the context, which emphasizes the importance of rigorous in vivo analyses to ascertain function. Here, we review the basic research and clinical findings that underlie the roles of cathepsins in cancer, and provide a roadmap for the rational integration of cathepsin-targeting agents into clinical treatment.

PMID:
26597527
DOI:
10.1038/nrc4027
[Indexed for MEDLINE]

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