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Tumour endoproteases: the cutting edge of cancer drug delivery?

Atkinson, J.M; Siller, C.S; Gill, J.H

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Authors

J.M Atkinson

C.S Siller

J.H Gill



Abstract

Despite progression in anticancer drug development and improvements in the clinical utilization of therapies, current treatment regimes are still dependent upon the use of systemic antiproliferative cytotoxic agents. Although these agents are unquestionably potent, their efficacy is limited by toxicity towards 'normal' cells and a lack of tumour selective targeting, resulting in a therapeutic index which is modest at best. Consequently, the development of more tumour selective cancer treatments, with better discrimination between tumour and normal cells is unequivocally an important goal for cancer drug discovery. One such strategy is to exploit the tumour phenotype as a mechanism for tumour-selective delivery of potent therapeutics. An exciting approach in this area is to develop anticancer therapeutics as prodrugs, which are non-toxic until activated by enzymes localized specifically in the tumour. Enzymes suitable for tumour-activated prodrug development must have increased activity in the tumour relative to non-diseased tissue and an ability to activate the prodrug to its active form. One class of enzyme satisfying these criteria are the tumour endoproteases, particularly the serine- and metallo-proteases. These proteolytic enzymes are essential for tumour angiogenesis, invasion and metastasis, the major defining features of malignancy. This review describes the concept behind development of tumour-endoprotease activated prodrugs and discusses the various studies to date that have demonstrated the huge potential of this approach for improvement of cancer therapy.

Citation

Atkinson, J., Siller, C., & Gill, J. (2008). Tumour endoproteases: the cutting edge of cancer drug delivery?. British Journal of Pharmacology, 153(7), 1344-1352. https://doi.org/10.1038/sj.bjp.0707657

Journal Article Type Article
Publication Date Apr 1, 2008
Deposit Date Jan 4, 2013
Publicly Available Date Mar 29, 2024
Journal British Journal of Pharmacology
Print ISSN 0007-1188
Electronic ISSN 1476-5381
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 153
Issue 7
Pages 1344-1352
DOI https://doi.org/10.1038/sj.bjp.0707657
Keywords Cancer therapy, Endoprotease, Prodrug, Drug delivery, Matrix metalloproteinase (MMP), Prostate-specific antigen (PSA), Cancer pharmacology.

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