# Bacterial Therapy of Cancer: A Way to the Dustbin of History or to the Medicine of the Future?
## 5 Bacteria in Cancer Therapy
### Scientists' Favorite \"Toys\" in Looking for a Panacea
This strain can be attenuated by eliminating a residential phage-carrying \(\alpha\)-toxin, which is responsible for toxicity. The spore-forming ability of clostridia is especially promising. Surviving as the spores in the oxygen environment, they germinate inside the tumor, causing hemorrhagic necrosis, cell lysis, and tumor regression. To date, the attenuated _C. novyi-NT_ strain has positively undergone phase I and II of clinical trials [76; 77]. A case was described where _C. novyi-NT_ spores were intravenously injected into the patient with advanced leiomyosarcoma, which was followed by complete tumor regression [78; 79]. Moreover, _C. novyi-NT_ was reported to reduce glioblastoma growth induced in rats [80]. _Salmonella_ sp. are Gram-negative, facultative anaerobic bacteria. They are able to move by flagella, facilitating their active migration from the vasculature into the deep tumor tissues. The most studied is _Salmonella enterica_ serovar _Typhimuriumum_ (_S. typhi_), an etiological agent of typhoid fever. In anticancer therapies, the attenuated strain of _S. typhi_ VNP20009 is used for safety reasons, to avoid the dissemination into healthy organs such as the spleen or liver. VNP20009 is attenuated by the chromosomal deletion of the genes _purl_ (purine) and _msbB_ (lipid A). Clinical trials on the use of this microorganism for melanoma treatment began in 2002, and to date have gone through phase I. In addition, the VXM01 antitumor vaccine, which is based on the attenuated strain of _S. typhi_, has successfully passed phase I clinical trials [81; 82; 83]. Other bacteria, in addition to the above, were also recruited in anticancer therapy [84]. Among the Gram-positive bacteria, these are, in addition to clostridia, _Listeria monocytogenes_, lactic acid bacteria, bifidobacteria, and _B. subtilis_. Attempts are being made to employ some of these as direct anticancer agents, while others are to be used as vaccines or as vectors for drug delivery. Bifidobacteria and _Lactobacillus_ are probiotic strains naturally found in the human gut. Oral administration of natural nonpathogenic _L. lactis_ is used as a prominent therapeutic agent to treat inflammatory bowel disease and moderate ulcerative colitis. An extensive study on _Listeria monocytogenes_ was focused mostly as a vaccine; moreover, some groups have used it as a gene-delivery vector for cancer therapy [85]. Among the Gram-negative bacteria following _S. typhimuriumum_ is _E. coli. E. coli_ strains are commonly nonpathogenic, in contrast to _S. typhi_, and can be found in the human gut. The latter makes it possible to use some _E. coli_ strains without attenuation. It was shown that _E. coli_ has the ability to colonize tumors in mice at a higher rate compared to normal tissues [86; 87]. The most widespread probiotic strain in use is _E. coli_ Nissle 1917, and also the wild-type MG1655 strain. Another Gram-negative species, _Pseudomonas aeruginosa_ strain 1409, was exerted, as it was demonstrated to have a good therapeutic effect in the mouse TC-1 tumor model. It is worth noting, however, that this bacterium is highly pathogenic for humans and often highly resistant to basic antibiotics, so it is probably not very suitable for the direct treatment of cancer [88; 89]. Not all mechanisms of the \"anticancer\" action have yet been adequately studied, but some are already known or suspected. They will be briefly discussed in the next section.