Perspectives
Nature Reviews Cancer 7, 870-879 (November 2007) | doi:10.1038/nrc2247
Opinion: Carboxypeptidase G2-based gene-directed enzyme–prodrug therapy: a new weapon in the GDEPT armoury
Douglas Hedley1, Lesley Ogilvie1 & Caroline Springer1 About the authors
Abstract
Gene-directed enzyme–prodrug therapy (GDEPT) aims to improve the therapeutic ratio (benefit versus toxic side-effects) of cancer chemotherapy. A gene encoding a 'suicide' enzyme is introduced into the tumour to convert a subsequently administered non-toxic prodrug into an active drug selectively in the tumour, but not in normal tissues. Significant effects can now be achieved in vitro and in targeted experimental models, and GDEPT therapies are entering the clinic. Our group has developed a GDEPT system that uses the bacterial enzyme carboxypeptidase G2 to convert nitrogen mustard prodrugs into potent DNA crosslinking agents, and a clinical trial of this system is pending.
Author affiliations
- Douglas Hedley, Lesley Ogilvie and Caroline Springer are at the Institute of Cancer Research Haddow Laboratories, 15, Cotswold Road, Sutton, Surrey, UK.
Correspondence to: Caroline Springer1 Email: caroline.springer@icr.ac.uk
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