The tumor resists therapies such as antibiotic bacteria


JUST LIKE THE BACTERIA, when they are put under stress by antibiotics, they change their DNA to continue growing despite the therapy, the tumor cells 'equip themselves' to resist the attack even of the latest generation drugs such as those targeted by molecules. In practice, they mimic the defense strategy used by bacteria against antibiotics. This is the discovery made by the Candiolo Fpo-Irccs Institute and published today in the journal Science.

The (inevitable) problem of resistance

It is almost a 'practice' that the tumor, even after a prolonged clinical response, becomes resistant to drugs and sometimes more aggressive than before. This also happens with precision medicine that customizes therapy based on the molecular characteristics of the individual tumor and the individual patient, to maximize benefits and reduce side effects. "It is commonly accepted that resistance develops: the patient responds for a while but then at some point the cancer returns," he says Alberto Bardelli, professor of the Oncology Department of the University of Turin at the Candiolo Fpo-Irccs Institute. "This happens because a small number of cells resistant to therapy is already present in the tumor mass, even before the drug is administered. In other words, resistance, and therefore the failure of therapy, is an inevitable fact ".

How the tumor fits

The results just published in the journal Science of a study supported by the Piedmontese Foundation for Cancer Research and by the Airc Foundation, reveal that drug-resistant cells are not always already present. Sometimes tumors, subjected to the stress generated by molecular-targeted therapies, "adapt" and change their genetic makeup by acquiring new mutations, which allow the cancer to survive therapies.

Tumors like infectious diseases

The researchers drew inspiration from 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. "We asked ourselves – they explain Alberto Bardelli is Mariangela Russo, researcher at the Candiolo Fpo-Irccs Institute – if we could not learn something from antibiotic resistance and thus studying how bacteria become resistant to antibiotics we realized that most when they have to deal with the drug try to mutate to survive, as a kind of survival instinct ".Then the researchers tried to understand if the same ruse could also be exploited by tumors. "We have observed – continues Bardelli – that a fraction of intestinal tumor cells stops growing, but is able to survive the siege of target therapies". The mechanisms regulating DNA repair are modified in the besieged cells; this leads to an accumulation of mutations, which are no longer recognized and corrected. This process is called adaptive mutagenesis. In other words, mutate to adapt, change to survive: in the presence of molecular-target therapies, cancer cells accumulate mutations until they become resistant to treatment, thus leading to the relapse of the disease.

New therapeutic targets are being studied

For now this research has focused on tumors of the intestine to which Professor Bardelli has been working for over ten years, but it remains to be seen whether the same "plan" applies to other types of cancer. What scenarios and therapeutic possibilities open up after this discovery? If resistance to therapies is not something inevitable, but is linked to a process that is activated during the treatment itself, 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, thus prolonging drug efficacy and survival of cancer patients. "The goal of all anti-cancer drugs is to prevent cancer cells from dividing. Without prejudice to the need to continue to use these therapies, we now want to try to develop drugs that do not reduce the proliferative capacity of cancer but that prevent mutagenicity so that the oncologist does not start off-beat in the fight against the disease but can count on an extra weapon ", concludes Bardelli.

"Airc research days"

Meanwhile, the various initiatives of the Airc Foundation continue to inform the public about the latest advances in cancer research and gather new resources to be allocated to the work of the researchers. Saturday, November 9th, the Foundation's volunteers will be present in over 1,000 squares to distribute Research Chocolates and collect new resources to be allocated to the approximately 5,000 researchers working on projects supported by Airc. In the face of a minimum donation of 10 euros it will be possible to receive a packet with 200 grams of dark chocolate, a food that taken in small quantities can bring benefits, as explained Antonio Moschetta, Airc scientist of the University of Bari: "A study conducted by an Italian research group, on a population of almost 11 thousand subjects, showed that the consumption of about 20 grams of dark chocolate every two days is able to reduce levels of circulating inflammation.This is very important given the relationship between inflammation and cancer. A moderate consumption of low-sugar dark chocolate could therefore represent a further possibility to reduce the role of systemic inflammation in aggression and tumor growth ". Along with the box of chocolates, the special Guide with valuable information on cancer prevention, diagnosis and treatment will also be distributed. From November 11th, the Chocolates of Research will also be available in 1,728 branches of Banco BPM, an institutional partner of AIRC that involves employees and customers to support the careers of young talents of Italian oncology.

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