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Gene directed enzyme/prodrug therapy of cancer: Historical appraisal and future prospectives
Author(s) -
Greco Olga,
Dachs Gabi U.
Publication year - 2001
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/1097-4652(2001)9999:9999<::aid-jcp1060>3.0.co;2-h
Subject(s) - prodrug , cytosine deaminase , thymidine kinase , genetic enhancement , ganciclovir , nitroreductase , suicide gene , gene delivery , herpes simplex virus , cancer research , biology , pharmacology , gene , computational biology , chemistry , biochemistry , virology , virus , human cytomegalovirus
Gene therapy of cancer is a novel approach with the potential to selectively eradicate tumour cells, whilst sparing normal tissue from damage. In particular, gene‐directed enzyme prodrug therapy (GDEPT) is based on the delivery 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 been investigated so far, 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 strategies. The most widely used enzyme/prodrug combinations already in clinical trials (e.g., herpes simplex 1 virus thymidine kinase/ganciclovir and cytosine deaminase/5‐fluorocytosine), as well as novel approaches (carboxypeptidase G2/CMDA, horseradish peroxidase/indole‐3‐acetic acid) are described, with a particular attention to translational research and early clinical results. J. Cell. Physiol. 187:22–35, 2001. © 2001 Wiley‐Liss, Inc.