Cutaneous melanoma is the deadliest of all skin cancers, mainly due to its tendency to invade and metastasize. It is the third malignant tumor, after that of the lungs and breast, to colonize mainly the brain. And without any therapeutic intervention, metastatic lesions lead to a survival of less than seven months. But the good news comes from Israel: Researchers have deciphered the mechanism that allows skin cancer to reach the brain and have been able to delay its spread by 60% to 80%, using an existing treatment.
A study with important potential
The discovery of the professor’s guided laboratory Ronit Satchi-Fainaro Tel Aviv University was born from the study launched five years ago by the Italian researcher Sabina Pozzi, in collaboration with the University of Turin, the American National Institutes of Health and Johns Hopkins University. The data has just been published on the Journal of Clinical Investigation Insight and welcomed with enthusiasm: even if it is still a pre-clinical study, it has the potential to be tested on humans and represents a concrete hope for the most serious cases of melanoma.
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Current treatments, including radiotherapy, chemotherapy, and targeted therapies, have increased survival by nearly 85%. Recent advances in immunotherapy have also improved the prospects for treatment. However, more and more frequently there is a lot of heterogeneity in metabolic responses and resistance to treatments. Now the discovery of the mechanism by which skin cancer sends metastases into the brain paves the way for new treatments also because it is based on a process already known and responsible for other pathologies.
The signals that the tumor sends to expand
“We found that already at the first stage melanoma begins to send signals to the astrocytes, thus preparing them for the dissemination of metastases in the brain – explains the professor. Anna Scomparin, pharmacologist of the University of Turin, in these days in Tel Aviv for the presentation of the important results achieved and to set the next steps of the research, aimed at the creation of a protein vaccine. it is decisive with an excellent prognosis. When metastases spread to the brain, radiation therapy may not be enough. And discovering the involvement of astrocytes is good news because there are already drugs capable of inhibiting them “.
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The central nervous system
Astrocytes are star-shaped cells that are part of the central nervous system. They are responsible for homeostasis and the preservation of brain physiology. They help the brain stay healthy, providing nourishment and support for neurons, and are the first to intervene in the event of a stroke or trauma. But melanoma is able to “corrupt” them already at an early stage of the disease, making them pass over to the side of the “bad guys”. In short, the tumor manages to make them become his allies, paving the way to the brain. That is why at an advanced stage, 90% of patients have brain damage.
A staggering statistic
“This is a disconcerting statistic – says the professor Satchi-Fainaro -: we expect to see more metastases in the lungs and liver while they were in the brain, which should be the most protected organ. “Normally the blood brain barrier prevents harmful substances from entering the brain, but” in this case it did not do its thing. work and we wondered how it was possible. “Once the flaw in the system came to light, it is already possible today to run for cover with drugs that are used for other pathologies, such as multiple sclerosis and other neurodegenerative diseases.
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“The communication between tumor and astrocytes is reflected in the fact that brain cells begin to secrete a protein that promotes inflammation – explains Professor Scomparin in detail -. Starting from this hypothesis we tested in vitro and with 3D computer simulations the action of bindarit, a drug that acts specifically on these receptors, preventing the establishment of this process which has already been associated with the pathogenesis of many inflammatory diseases, in the hope that it could also block metastases “. And so it was. “This specific drug is not yet on the market but is the subject of a phase two clinical study in patients with diabetic nephropathy, so if it is approved it will be easier to test it even in patients with advanced melanoma.” But that’s not the only cure.
“To block the receptor – continues Scomparin – monoclonal antibodies can also be effective. The in vitro results have been very promising but the road is long. The other way is vaccines“. Researchers in Professor Satchi-Fainaro’s laboratory already developed a nano-vaccine two years ago with positive effects in the prevention and treatment of primary and metastatic tumors tested on mice. Now the goal is to create one for humans – concludes the expert, “to be used in combination with immunotherapy based on checkpoint inhibitors, which have already proved effective and are part of the current therapeutic protocol” .
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