Cysteine cathepsins as a prospective target for anticancer therapies—current progress and prospects

Cysteine cathepsins (CTS), being involved in both physiological and pathological processes, play an important role in the human body. During the last 30 years, it has been shown that CTS are highly upregulated in a wide variety of cancer types although they have received a little attention as a pote...

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Bibliographic Details
Published in:Biochimie 2018-08, Vol.151, p.85-106
Main Authors: Pogorzelska, Aneta, Żołnowska, Beata, Bartoszewski, Rafał
Format: Article
Language:English
Subjects:
Animals
Anticancer therapies
Antineoplastic Agents - therapeutic use
Cathepsins
Cathepsins - metabolism
Cathepsins - pharmacology
Cystatins
Cysteine - metabolism
Cysteine cathepsins
Humans
Inhibitors
Neoplasms - drug therapy
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Summary:Cysteine cathepsins (CTS), being involved in both physiological and pathological processes, play an important role in the human body. During the last 30 years, it has been shown that CTS are highly upregulated in a wide variety of cancer types although they have received a little attention as a potential therapeutic target as compared to serine or metalloproteinases. Studies on the increasing problem of neoplastic progression have revealed that secretion of cell-surface- and intracellular cysteine proteases is aberrant in tumor cells and has an impact on their growth, invasion, and metastasis by taking part in tumor angiogenesis, in apoptosis, and in events of inflammatory and immune responses. Considering the role of CTS in carcinogenesis, inhibition of these enzymes becomes an attractive strategy for cancer therapy. The downregulation of natural CTS inhibitors (CTSsis), such as cystatins, observed in various types of cancer, supports this claim. The intention of this review is to highlight the relationship of CTS with cancer and to present illustrations that explain how some of their inhibitors affect processes related to neoplastic progression. Cysteine cathepsins (CTS) are involved in tumor development and metastasis. Hence, cysteine cathepsin inhibitors are considered to constitute promising therapeutics in cancer treatment. [Display omitted] •Cysteine cathepsins (CTS) are highly upregulated in various types of cancer.•Inhibition of CTS becomes an attractive strategy for cancer therapy.•Cystatins, endogenous CTS inhibitors, may control tumor progression.•Exogenous inhibitors of cysteine cathepsins are a lead for new anticancer drugs.
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2018.05.023