Recent developments in gene-directed enzyme prodrug therapy (GDEPT) for cancer.
Gene-directed enzyme prodrug therapy (GDEPT) is a promising two-step treatment for solid malignant tumors. In the first step, the gene for a foreign enzyme is administered and directed to the tumor, where it may be expressed using specific transcriptional elements. In the second step, prodrugs are administered and activated by the foreign enzyme expressed at the tumor. This review focuses on the progress from the end of 1997 to date. Important issues, such as viral and non-viral vectors, new enzyme/prodrug systems, new strategies, advances in the understanding of the bystander effects, the comparison of different systems used in GDEPT and clinical trials are outlined.
Niculescu-Duvaz
I
I
CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK.
Cooper
R G
RG
Stribbling
S M
SM
Heyes
J A
JA
Metcalfe
J A
JA
Springer
C J
CJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001711:Biotransformation; D024201:Bystander Effect; D002986:Clinical Trials as Topic; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D043525:Cytosine Deaminase; D000229:Dependovirus / Q000235:genetics; D004337:Drug Carriers; D004789:Enzyme Activation; D004790:Enzyme Induction; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use; D005544:Forecasting; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000627:therapeutic use; D008081:Liposomes; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009700:Nucleoside Deaminases / Q000235:genetics / Q000378:metabolism; D011355:Prodrugs / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012190:Retroviridae / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D011623:gamma-Glutamyl Hydrolase / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D004337:Drug Carriers; D004798:Enzymes; D008081:Liposomes; D011355:Prodrugs; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D003577:Cytochrome P-450 Enzyme System; D013937:Thymidine Kinase; D011623:gamma-Glutamyl Hydrolase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D005472:Fluorouracil