Tumour endoproteases: The cutting edge of cancer drug delivery?

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

Research output: Contribution to journalReview article

39 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1344-1352
Number of pages9
JournalBritish Journal of Pharmacology
Volume153
Issue number7
DOIs
StatePublished - Apr 1 2008

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Pharmaceutical Preparations
Neoplasms
Prodrugs
Enzymes
Therapeutics
Cytotoxins
Serine Proteases
Drug Discovery
Peptide Hydrolases
Neoplasm Metastasis
Phenotype

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Atkinson, J. M. ; Siller, C. S. ; Gill, J. H. / Tumour endoproteases : The cutting edge of cancer drug delivery?. In: British Journal of Pharmacology. 2008 ; Vol. 153, No. 7. pp. 1344-1352.
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Tumour endoproteases : The cutting edge of cancer drug delivery? / Atkinson, J. M.; Siller, C. S.; Gill, J. H.

In: British Journal of Pharmacology, Vol. 153, No. 7, 01.04.2008, p. 1344-1352.

Research output: Contribution to journalReview article

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