Despite the large number of various anti-cancer drugs on the market, cancer remains one of the most deadly diseases worldwide with the number of cases steadily increasing. Among the most promising, more recent developments are directed enzyme prodrug therapies. All directed enzyme prodrug therapies operate with the same basic concept: a nontoxic prodrug is converted into a toxic drug inside of cells which were transformed with a gene construct (GDEPT) or bacteria (BDEPT) encoding the enzyme needed for the prodrug/drug conversion or antibody (ADEPT) as antibodyprodrug/ drug converting enzyme fusion proteins. Recently, several genera of bacteria have been shown to specifically accumulate and replicate within tumors, including Clostridium, Salmonella, Bifidobacterium, Listeria and E. coli. These bacteria can cause cancer cell death by competing for nutrients and/or by secreting toxic bacterial products. In BDEPT method, that has even been used in pilot trials for refractory cancer patients, some of these bacteria are utilized as specific gene delivery vehicles for selective enzyme activation of prodrugs at the tumor microenvironment to increase treatment specificity. Recently, Salmonella expressing carboxypeptidase G2, Escherichia coli expressing β -glucuronidase (βG), Salmonella expressing herpes simplex virus thymidine kinase, Salmonella expressing E. coli cytosine deaminase (CD) and Listeria expressing purine nucleoside phosphorylase (PNP) have been shown to generate potent and selective antitumor activity by converting systemically administered prodrugs to active anticancer agents in various types of tumors, while minimizing exposure of normal tissues to active drugs. Bacteria-directed enzyme prodrug therapy (BDEPT) is a promising therapeutic approach for treatment of some solid tumors. Optimization and improvement of the selected prospective model type of BDEPT would help to improve the development of bacterial-mediated cancer treatment and drug delivery systems and their successful applications in future clinical trials.

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