Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25338741
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25338741
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 AAPS+J
2015 ; 17
(1
): 102-10
Nephropedia Template TP
AAPS J
2015[Jan]; 17
(1
): 102-10
PMID25338741
show ga
As one targeting strategy of prodrug delivery, gene-directed enzyme prodrug
therapy (GDEPT) promises to realize the targeting through its three key features
in cancer therapy-cell-specific gene delivery and expression, controlled
conversion of prodrugs to drugs in target cells, and expanded toxicity to the
target cells' neighbors through bystander effects. After over 20 years of
development, multiple GDEPT systems have advanced into clinical trials. However,
no GDEPT product is currently marketed as a drug, suggesting that there are still
barriers to overcome before GDEPT becomes a standard therapy. In this review, we
first provide a general introduction of this prodrug targeting strategy. Then, we
utilize the four most thoroughly studied systems to illustrate components,
mechanisms, preclinical and clinical results, and further development directions
of GDEPT. These four systems are herpes simplex virus thymidine
kinase/ganciclovir, cytosine deaminase/5-fluorocytosine, cytochrome
P450/oxazaphosphorines, and nitroreductase/CB1954 system. Later, we focus our
discussion on bystander effects including local and distant bystander effects.
Lastly, we discuss carriers that are used to deliver genes for GDEPT including
virus carriers and non-virus carriers. Among these carriers, the stem cell-based
gene delivery system represents one of the newest carriers under development, and
may brought about a breakthrough to the gene delivery issue of GDEPT.
free
free
free
