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Instead of resorting to chemotherapy, and if we were inspired by the defense mechanisms of our body to fight cancer? Following this idea, American researchers have discovered a way to push cancer cells to suicide.
Cure cancer by causing the suicide of malignant cells, but without reaching others, this is what propose new American work published in eLife and Nature Communications. These are based on molecules naturally used by cells to regulate the use of genes. Still in the fundamental state, these results make it possible to identify a particular molecule that could possibly eventually replace chemotherapy.
Every day, randomly, potential mutations suffered by our DNA at the time of its duplication or under the effect of different substances, many cells are born nonfunctional in our body. Some of them acquire dangerous properties: they multiply anarchically or can escape the immune system. Features that could cause cancer. Fortunately, each of our cells has a capacity called "apoptosis": this is cell suicide. Cells can indeed detect themselves as non-functional and activate genes leading to their destruction. For this, they synthesize small molecules that will bind to certain RNA (intermediate to translate DNA into proteins) to destroy it. These small molecules are in fact RNAs, called interfering RNAs, whose sequence is complementary – and therefore specific – to that of the targeted RNA.
Forcing the cancer cell to commit suicide
But truly cancerous cells are the few that have acquired additional capacity by mutation: that of not being able to trigger apoptosis. However, the genetic sequences for activating these interfering RNA exist. To activate them, it is possible to use chemotherapy. However, these are heavy treatments with many side effects, which also attack some healthy cells. Researchers at Northwestern University in Chicago therefore came up with the idea of directly bringing interfering RNAs to reactivate apoptosis to cancer cells.
In work published in 2017, the team began by showing that cancer cells die after introduction of certain interfering RNAs. The problem with cancer cells is that they multiply so quickly that they can develop resistance to the treatments that kill them, in the manner of bacteria against antibiotics. Here, however, the team found that cancer cells treated with RNA molecules never became resistant! Because the effect of these interfering RNA is so fast that they simultaneously eliminate several genes they need to survive. The cells can become resistant to one mechanism of action, but not to several different simultaneously. "It's like committing suicide by stabbing yourself, firing at each other and jumping from one building at the same time. You can not survive", Says in a statement Marcus E. Peter, lead author of the publication. The team even discovers that there is no need to use a whole interfering RNA, but just a very short fragment of only 6 nucleotides (constituent elements of DNA and RNA).
Exceed the natural mechanisms of fight against cancer
In the latest work published in 2018, Pr Peter's team tested the 4,096 different combinations of this sequence of 6 nucleotides until finding the most toxic for cancer cells (human and mouse). Surprisingly, they found a sequence that actually exists (in small quantities, however) in our body as a mechanism to fight cancer! A defense mechanism developed 800 million years ago by cells, according to scientists. By digging a little more of the mechanism of action, they discovered that cells cut a gene involved in cell growth into small pieces. Fragments that then became highly toxic to cancer cells. According to the researchers, nearly 3% of the RNAs of the cell could be thus cut! "Based on what we learned in these two studies, we can now design even more potent artificial microRNAs against cancer cells than those developed by nature"Said Marcus E. Peter. A process that will take many more years. (Sciencesetavenir)
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