J.M Atkinson
Tumour endoproteases: the cutting edge of cancer drug delivery?
Atkinson, J.M; Siller, C.S; Gill, J.H
Authors
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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Copyright Statement
The definitive version is available at http://onlinelibrary.wiley.com
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