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.
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Thank you to Frank Friedlos for the immunofluorescence experiments. This work is funded by Cancer Research UK (grant numbers C309/A2187 and C309/A8274).
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Hedley, D., Ogilvie, L. & Springer, C. Carboxypeptidase G2-based gene-directed enzyme–prodrug therapy: a new weapon in the GDEPT armoury. Nat Rev Cancer 7, 870–879 (2007). https://doi.org/10.1038/nrc2247
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