ADVANCED DRUG-DELIVERY REVIEWS - ENZYME PRODRUG THERAPY

Enzymes have provided a focus for the chemist to design a range of pro drugs to release cytotoxic agents already in use in the cancer clinic and those which had been candidates in the past, based on their effica cy in preclinical studies, but discarded because of their toxicity to normal tissues. The specificity of enzyme reactions provides the means to limit prodrug activation to the tumour site, through enzyme target ing by chemical conjugation or genetic fusion to tumour associated ant ibodies (ADEPT), or via enzyme gene delivery systems into tumour cells (GDEPT). The substrate tolerance of many of the enzymes used has also meant that a variety of prodrug/drug combinations can be assessed usi ng the same enzyme reaction. It is the flexibility provided by the cho ice of enzyme, the range of tumour antigen targets and the prodrug che mistry that makes ADEPT such an exciting prospect for the future of ca ncer treatment and the more recent extension of the enzyme/prodrug con cept to a gene therapy approach provides a second avenue for success.