"The tumor resists cancer drugs such as antibiotic bacteria"


It is called "blue moon research", meaning to venture where no one has yet set foot. When research explores fields that are not yet beaten, the results can be even more important. The study started in Candiolo three years ago is a concrete example of "blue moon" research and now the magazine Science publishes the work carried out with the support of the Piedmontese Foundation for Cancer Research and the AIRC Foundation, a survey started three years ago gives an insight into the behavior of bacteria when they are attacked by antibiotics. Mariangela Russo and Alberto Bardelli, researcher and professor of the Department of Oncology of the University of Turin who work at the Candiolo FPO-IRCCS Institute, were inspired by a phenomenon that occurs in the field of infectious diseases. Under the stress of antibiotics, bacteria temporarily increase the ability to mutate their DNA, acquiring new mutations that allow them to grow despite therapy. Sometimes, subjected to the stress generated by molecular-targeted therapies, even tumors "adapt" and change their genetic makeup by acquiring new mutations that allow cancer to survive therapies.Could the same ploy adopted by the bacteria be exploited even by tumors? The question from which the deepening party in Candiolo (special observed for the moment is colon cancer) originated has had a positive response. A team of thirty people, molecular biologists, oncologists, mathematical engineers, geneticists and bioinformatics contributed to the research. Very different training and a common goal that allowed for a 360 degree observation. It has been observed that a fraction of intestinal tumor cells stops growing, but is able to survive the siege of therapies. In the besieged cells the mechanisms that regulate DNA repair are modified and this leads to an accumulation of mutations, which are no longer recognized and corrected. The process is called adaptive mutagenesis: mutating to adapt, change to survive. In the presence of molecular target therapies, tumor cells accumulate mutations until they become resistant to treatment. The consequence is the return of the disease, the feared recurrence. "Cancer resists therapies like antibiotic bacteria," explains Alberto Bardelli
So far it was believed that the return of the tumor, often more aggressive than before, was inevitable, because within the tumor mass there is a small number of cells resistant to therapy. The study reveals that this is not always the case.

If resistance to therapies is not always an inevitable fact, but is linked to a process that is activated during treatment, then hitting the mechanisms underlying adaptive mutagenesis could increase the chances of success of drugs already in use. Turin researchers are already working to identify new therapeutic targets in the near future in the process of adaptive mutagenesis that may slow down, or perhaps even prevent, the onset of resistance to therapies. A new class of drugs, used so far for the protection of DNA. The effectiveness of the drugs can be prolonged with significant consequences on the survival of the patients. Bardelli tomorrow (November 8th) will be in London to present the results of the study at the Congress of the European Society of medical oncology: "An all-Italian study, an aspect not so common".

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