# 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  
For more than one hundred years since [PERSON]'s toxin, which was the first anticancer microbial \"vaccine\" based on a mixture of _Streptococcus pyogenes_ and _Serratia marcescens_, many microorganisms have been studied for their antitumor activities (see Section 2). Some bacteria-based preparations were used, and continue to be used today, as a therapy complementary to standard treatment, increasing the patient's chances of recovery. Not every microorganism is suitable for the role of an anticancer \"vaccine\". To be useful as an antitumor therapeutic agent, the bacterium should be: (1) Sufficiently invasive; that is, enter the tumor and survive and accumulate in it. (2) Safe for the patient--at least no more harmful than the cancer itself. To achieve this, it can use human commensal bacteria, which already live in the human body, or take pathogenic bacteria deprived of virulence factors (attenuated). (3) A microorganism that has completed its antitumor mission should be easily killed by an antibiotic--and, therefore, it should be sensitive to antibiotics, or should not easily acquire resistance to drugs. (4) The microorganism that can affect the tumor in different ways. It can be immunogenic, that is, it can stimulate a good immune response in a macroorganism, or it can produce some agents (toxins) that directly affect the tumor cells, killing them. Finally, the bacterium can be convenient for genetic manipulation to give it the desired properties--for example, the carrier of antitumor drugs. For the long history of \"bacterial anticancer therapy\", bacteria could be used both as a natural, wild-type strains and attenuated or genetically modified species; the last has been made for improving the natural ability of bacteria for the preferential colonization of tumors and creating a precisely controlled and highly specific nonpathogenic delivery shuttle. Thus, for example, the bacillus Calmette-Guerin (BCG) is widely applied. BCG is a strain of _Mycobacterium bovis_ which has been used for a hundred years as a tuberculosis vaccine. This microorganism--an etiological agent of bovine tuberculosis--was intentionally attenuated by many passages until it became an avirulent, but immunogenic, strain safe for human use. The links between the occurrence of tuberculosis and cancer regression were noted quite a long time ago, and in the last quarter of the 20 th century, BCG was approved as the complementary treatment of bladder cancer. Treatment with the _M. bovis_ BCG strain is considered effective when the intravesical infusion of the microbial suspension using urethral catheters is used [73; 74]. The particular attention of researchers has long been attracted to anaerobic bacteria, such as _Clostridium_ spp., _Salmonella_ spp., and _Listeria_ spp. The conditions inside the tumor are hypoxic, since the tumor is vascularized mostly from the outside. Therefore, the conditions inside the tumor are quite favorable for the development of obligate or facultative anaerobes. The greatest advantage of using these microorganisms is that they have a tendency to concentrate directly inside the tumor, in contrast to chemotherapeutics which spread throughout the body with the blood, also destroying normal, healthy cells [75]. The most common type of bacteria in use is probably _Clostridium_. The history of _Clostridium_ as a fighter against cancer started in 1935, when an article was published describing the regression of advanced cancer under the use of sterile filtrates with _Clostridium_ [72]. _Clostridium_ spp. is one of the largest prokaryotic genera, consisting of a heterogeneous group of Gram-positive, strictly anaerobic, spore-forming rods. Over the past decades, many studies have been conducted on the use of different clostridium species--_C. histolytica_, _C. tetani_, _C. octolyticum_, _C. beijenrtickii_, and _C. novyi_--as tumor-targeting agents. One of the most promising is considered a genetically modified _Clostridium novyi-NT_ strain.