Cancer treatments began with aggressive chemical cocktails and evolved with the creation of drugs from cells. Now, living beings can be incorporated into the war against these diseases. A few days ago, a team of researchers from the universities of San Diego (USA) and Adelaide (Australia) presented in the magazine Science a work in which modified bacteria were used to detect tumor DNA in the intestines of mice. This capacity could be incorporated into those explored by other projects, which have managed to use bacteria designed to carry therapeutic loads to the interior of solid tumors, overcoming the barriers with which they protect themselves from the immune system and the difficulties in reaching them with medications.
The authors of the work adapted an ability of bacteria to adapt to their environment known as horizontal gene transfer. Faced with the vertical transmission that occurs between parents and children, microorganisms are capable of exchanging genes, and the capabilities they provide, between them, something that facilitates, for example, the spread of resistance to antibiotics. Although this exchange ability between bacteria is known, the researchers saw that it is also possible between mammalian tumors or human cells and bacteria.
Among the bacteria that populate the intestine, Robert Cooper, from the University of California in San Diego, chose the Acinetobacter baylyi, an organism that they modified so that it could identify the mutated KRAS gene that is behind many tumors. The bacteria incorporated that DNA, which was later used to know if the mouse from which they had been extracted had developed a tumor. Researchers now want to use these bacterial biosensors to detect other types of tumor or some microbial infections.
Advances in synthetic biology are not only making it possible to recruit bacteria to warn that a tumor is lurking, they can also annihilate it. A team from Caltech (USA) has used bacteria directed with ultrasound to deliver drugs to tumors, taking advantage of their tricks to escape the immune system. Cancer cells are capable of generating an immunosuppressive environment that keeps cells such as T lymphocytes at bay, but in this way they make it easier for bacteria to settle there. The researchers modified the bacteria so that they transport drugs that would not otherwise reach them and, in addition, they developed an ultrasound system that activated the release of the drug only in the harmful cells, avoiding harmful effects on the healthy ones.
The authors of the article you publish Science They warn that their work is a proof of concept, but they already have ideas about how they could bring it to patients. “Management could be as easy as taking a probiotic pill [con las bacterias de diseno dentro]”explains Robert Cooper, first author of the article and researcher at the University of California, San Diego. The bacteria would then be extracted for analysis through stool, urine or blood samples.
Cooper recognizes that the limitations of this way of detecting tumor DNA are that bacteria only capture known mutations that they are designed to detect. “However, colorectal cancer tends to have a few very common mutations that trigger it,” he notes. Furthermore, the intestine is a place full of bacteria, the well-known intestinal microbiome, which makes it very easy to incorporate these biosensors into an environment that is welcoming to them. This characteristic would make this method superior in sensitivity to liquid biopsies, which require more time for a solid tumor to develop and begin to spread tumor DNA in the blood.
For the future, scientists want to expand the system so that it is possible to identify more than one mutation, incorporating new modifications to the bacteria or making cocktails with different bacteria that detect different mutations. “DNA detection will probably have to be combined with other screening methods, because not all tumors will have a different mutation, but it may at least be possible to reduce the frequency of colonoscopies,” concludes Cooper.
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Source: EL PAIS