Could the p53 protein that protects elephants from cancer be implanted in humans? | Science


Not only elephants have the p53 protein, we have all mammals. This protein has what we call a cancer suppressor gene, it is able to prevent the tumor from developing. What the news about the elephants that you are referring to described is that these animals, instead of having a copy of the gene of this molecule, have fifteen or twenty copies, that is, the amount of this protein that they produce is much greater than the that we can produce humans. The research you are referring to defends the hypothesis that the reason why elephants have very few tumors is precisely the high amount of this protein they produce.

But now, let's go to the answer to your specific question. The possibility of using this protein to fight cancer in people. The first thing I have to tell you is that this is a line of cancer research that has been very active for more than twenty years: trying to control p53 levels in tumors as a way to prevent them. It has been investigated, for example, in mice. What has been done is something similar to what happens to elephants, instead of having a single copy of the gene increase the number of copies and they are actually called super p53 mice. This was investigated by the scientist Manuel Serrano at the National Center for Oncological Research more than 15 years ago. And indeed he discovered that those mice are more protected against tumors.

But although it is a therapeutic strategy that is trying to develop for many years It is not as easy as you might think because the solution is not simply to increase p53 levels and that's it. This can not be done, first you have to look for methods that allow you to increase the protein without causing more problems than those that you try to correct.

And what could those methods be? There are several alternatives. The first thing that was tried was the use of modified viruses to increase the expression of the gene that codes for this protein and thus increase the production of the protein itself. They used adenoviruses that are a type of virus that do not integrate into the genome, by not integrating means that they are not maintained permanently, that can be an inconvenience but prevents the genome of the cell being manipulated from being altered. But the investigation discovered that this method did not work and this way is abandoned.

DNA chain.
DNA chain.

At present and for some time now, research has focused on knowing very well how this p53 molecule works. What we know about her is that it has a very small half-life, meaning that it is active very little time in the cell. For this reason, one of the research channels tries to keep it active longer so that it can exercise its function. And that is done by trying to block other molecules that are what make little time available in the cell.

We also know that in humans it is present at very low levels. To understand this avenue of research, it is necessary to know a little how p53 works. When the DNA of a cell is damaged, p53 is activated and has the ability to make if a cell is dividing but has suffered damage, you can tell the cell: stand up, do not keep dividing!, To prevent that damage is transferred to the daughter cells. The p53 protein gives the cell a signal to stop its cell division and thus gives the cell time to repair the damaged DNA, for example by the ultraviolet rays of the sun in excessive doses. He says: "No, no, you stand up and repair the DNA so you do not transmit that damage that can be a mutation". If the cell obeys, perfect, but if it does not, p53 gets the cell to die and thus prevents mutations from being transmitted. That is what happens in a normal cell. In the tumor cells what happens is that the p53 protein does not work as it has to work and the cell continues to divide and continues to accumulate mutations without repair. If we had a lot of normal protein this would block it. And that is why a great effort is being made to reach this situation, but until now it has not been achieved. There are ongoing clinical trials but they have not yet reached patients.

Another way of investigation is the use of the CRISPR technique of genetic editing. But since this is a protein that has a very important function in normal cells, it should be a CRISPR directed exclusively to the tumor cell. As far as I know, it has not yet been possible to put into practice but it is feasible that within a few years CRISPR technology will advance and can be done in a completely targeted way to these tumor cells and safely.

Amparo Cano is a professor in the Department of Biochemistry at the Autonomous University of Madrid, head of the Tumor Progression Mechanism group of the Alberto Sols Biomedical Research Institute, a CSIC-UAM mixed center.

Question done via email by María Gallardo Ruiz

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