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Page 6 of 25 Torres et al. J Cancer Metastasis Treat 2018;4:4 I http://dx.doi.org/10.20517/2394-4722.2017.49

Figure 3. Bacterial therapeutic mechanisms. Multiple bacterial features that can be used to make novel therapies against cancer. NK: natural killer

BACTERIA SUPPORTING THE FIGHT AGAINST CANCER: A CROSSROAD FOR GENETICS,
IMMUNOLOGY AND MICROBIOLOGY
Aiming for the perfect bacterium
Limited penetration in tumor tissue is considered a challenge for conventional therapy. This happens
to chemotherapy and other specific biological therapies. They all depend on passive transport of the
[8]
molecules into the tumor, limiting their efficacy and increasing their risk for toxicity . On the other
hand, bacterial therapy works through mechanisms against cancer that cannot be achieved with standard
[79]
conventional methods, becoming a great prospect .

The main issue with therapeutic uses of microorganisms against cancer in the 19th century was the
adverse effects associated to immunity, such as fever, septic shock, and death [80,81] . Development in
genetic engineering has led to use genetically modified bacteria- decreasing their pathogenicity- as
[82]
cancer therapy . Their accessible genome manipulation make bacteria the best candidates among
[83]
other microorganisms . Giving them the ability to enter cancerous tissue [82,84] , selecting tumor cells
following specific chemical signals in their microenvironment [85,86] and acting as vectors for molecule
transportation [87,88] assuming the fact they can be controlled from outside [Figure 3] [89-92] .

The “artificial medical bacteria” also have a role in the diagnostic process (detecting molecules or tumor
markers related to certain diseases), therapeutic decision making (detection of chemical stimuli and
[93]
production of therapeutic agents) and most importantly, can be controlled . Synthetic biology has been used
to design and build biologic machineries based on vehicles. Bacteria compounds integrated on genes, proteins
[94]
and molecules coming from multiple origins can affect their security and therapeutic effect . Systemic
administration of these compounds would be better. Less concentration would be needed and multiple agents
[93]
could be made without requiring neither formulation nor purification processes to amplify their effect .
Selective colonization in cancerous tissue
Blood supply in cancerous tissue is insufficient, which results in acidity, deprivation of nutrients and
[95]
presence of hypoxic areas . Hypoxia is more associated with expression of malignant phenotypes