2023-11-06 07:30:21
Researchers from the Institut Curie, Inserm and the CEA have highlighted the role of an enzyme in repairing breaks in the DNA of cancer cells. This discovery opens the way to the development of new treatments for breast and ovarian cancers. Clinical trials have already started.
DNA breaks in the cells of the human body are very common, because they are involved physiologically in all processes of cellular life. Maintaining the stability of this genetic material is essential for all cellular processes and by extension to keep the body healthy. It is estimated that almost half of breast and ovarian cancers are linked to failure of the biological systems that repair DNA breaks. Researchers from the Institut Curie, Inserm and the CEA have discovered the mechanism allowing cancer cells to repair their DNA. Their discovery, which was the subject of a publication in Natureopens the way to the development of new therapeutic targets.
“No living cell can live without repairing DNA breaks which occur very regularly,” explains Dr Raphaël Ceccaldi, Inserm researcher at the Institut Curie. This means that even cancer cells need to carry out this repair. Homologous recombination constitutes one of the main ways to repair these breaks, however cancer cells do not have access to it. We have succeeded in highlighting the alternative means that they use to repair their DNA. »
Scientists have demonstrated that it is an enzyme, called theta polymerase, also called PolꝊ, which intervenes where other DNA repair pathways do not work. Already in 2015, they had highlighted its important role, but without being able to decipher what its mechanism of action was. At the time, this first research work had already been the subject of a first publication in Nature.
Thanks to the understanding of the function of this enzyme, a new avenue for the treatment of breast and ovarian cancers appears. It consists of inhibiting this polymerase to prevent it from repairing DNA and thus having a deleterious effect on cancer cells. Researchers have demonstrated that inhibition of PolꝊ during cell division by mitosis prevents proper DNA repair and therefore leads to the death of cancer cells. By targeting only this alternative mechanism which is specific to cancer cells, the advantage of this therapeutic solution is that it is non-toxic for the patient’s non-tumor cells, whose DNA repair is carried out by the recombination pathway. counterpart. It is in this sense that it can be described as targeted therapy.
The first results of clinical trials are expected in 2024
Several laboratories did not wait to understand the role of this polymerase and as early as 2015, some began to develop inhibitors. “My laboratory developed one and I believe that a total of five were developed,” explains Dr. Raphaël Ceccaldi. Clinical trials are already underway and the first results should arrive in 2024. The arrival of this new method of treatment in the public therapeutic field will depend on the results of these trials, but understanding the mechanism of this polymerase reassures us in the idea that this medicine should work. »
The discovery of the role of this polymerase is an important step in understanding how cells in the human body control genome stability. For several decades, the dogma within the scientific community was that no DNA repair took place during cell division. Since the DNA was compacted during this phase, the researchers thought it was impossible. “Our discovery changes the vision of all these genome maintenance mechanisms,” adds Dr Raphaël Ceccaldi. It’s like opening a treasure box and it opens up a whole new field of exploration. It is quite complicated to predict what the discoveries will be or their importance, but it is almost certain that there will be more. In my laboratory, we will continue to study mitosis and we will probably discover other mechanisms and perhaps they will be important for, for example, other types of cancer or other diseases. »
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