O. Greco et Gu. Dachs, Gene directed Enzyme/Prodrug therapy of cancer: Historical appraisal and future prospectives, J CELL PHYS, 187(1), 2001, pp. 22-36
Gene therapy of cancer is a novel approach with the potential to selectivel
y eradicate tumour cells, whilst sparing normal tissue from damage. In part
icular, gene-directed enzyme prodrug therapy (GDEFT) is based on the delive
ry of a gene that encodes an enzyme which is non-toxic per se, but is able
to convert a prodrug into a potent cytotoxin. Several GDEPT systems have be
en investigated so Car, demonstrating effectiveness in both tissue culture
and animal models. Based on these encouraging results, phase I/II clinical
trials have been performed and are still ongoing. The aim of this review is
to summarise the progress made in the design and application of GDEPT stra
tegies. The most widely used enzyme/prodrug combinations already in clinica
l trials (e.g., herpes simplex 1 virus thymidine kinase/ganciclovir and cyt
osine deaminase/5-fluorocytosine), as well as novel approaches (carboxypept
idase G2/CMDA, horseradish peroxidase/indole-3-acetic acid) are described,
with a particular attention to translational research and early clinical re
sults. (C) 2001 Wiley-Liss, Inc.