Neurons can help treat cancer, study points out

The increase in neuronal activity reduced the development of melanoma, a type of skin cancer, by more than half the size, according to a study carried out with mice. It was also noticed that neurons collaborated with the increase of immune cells that are used to cure the disease.

The scientific article was published in the journal Acta Neuropathologica Communications and signed by researchers from different institutions, such as UFMG and Hospital Sírio Libanês.

According to Inca (National Cancer Institute), even though it represents only 3% of skin cancer cases in Brazil, melanoma is considered one of the most aggressive types of the disease because of the high possibility of proliferating throughout the body through metastasis.

2020 data from the institute showed that, on average, there were 8,450 new cases of the disease in the country. In 2019 alone, nearly 2,000 people died from this cancer.

For this study, the investigation was carried out specifically with sensory neurons, which perform functions such as the emission of pain signals and notions of temperature, explains Alexander Birbrair, professor at the Institute of Biological Sciences at UFMG and coordinator of the research.

These neurons have fibers that can extend through a large part of the human body and integrate with other organs, such as the heart. The first major finding of the research was that these branches also incorporated into melanoma.

“Almost half the makeup of a tumor is not cancer cells. It’s what we call the tumor microenvironment — various cells and components that migrate into the tumor, [como aconteceu com as fibras neuronais], and that manage to influence the behavior of cancer cells”, he says.

From there, the researchers used a technique called chemogenetics, which consists of using synthetic drugs together with genetic modifications to control neuronal activity.

In the case of mice, they were born genetically modified, so that, when they had contact with the drug CNO (Clozapine-N-oxide), they suffered a reduction or an overactivation in the activity of neurons that had fibers in the cancer.

“The finding was that when we completely turned off these neurons, the tumor swelled and the mouse lived less. Based on these initial results, we decided to overactivate these neurons so that they fire more than normal, and we saw that the tumor shrank,” says Birbrair.

Another finding of the study was that the exaggerated activation of neurons decreased blood vessels linked to cancer. According to Birbrair, the reduction in these vessels also helped to improve the disease because “a tumor needs oxygen and nutrients to grow and this comes through blood vessels”.

He points out that currently some therapies used against cancer are already based on shrinking blood vessels to shrink the tumor.

The researchers also noticed a third positive reaction as the activity of neurons increased — the number of immune cells that fight cancer increased, while the number of cancer cells decreased.

The use of these immune cells to treat cancer is known as immunotherapy — a method that “unmasks” the tumor so that the body starts fighting the disease. Thus, the expansion of this cell type demonstrates that “sensory neurons can promote an immune microenvironment and immune cells” against cancer, says Birbrair.

“We saw that sensory neurons are not working only as message carriers, which is their classic function. We are showing that these neuronal fibers performed proactive activities inside the tumor”, completes the professor.

The explanation for these positive effects against cancer needs further study, but the researchers may have found an answer — they noticed the proliferation of a molecule released by neurons called the “calcitonin gene-related peptide”.

“There was an increase in the generation of this peptide within the tumor with the overactivation of the neuron. When we inhibited it, there was a decrease in the peptide”, says Birbrair, highlighting the need for further studies to confirm or not this hypothesis.

The method of increasing neuronal activity also has the advantage of being more targeted when compared to other more toxic anticancer treatments. Chemotherapy, for example, corresponds to killing all the new cells growing in a certain region, which causes side effects in patients.

In the research, no serious side effects were detected in the mice that survived, says Birbrair.

If it is to be repeated in people, the study will need an adaptation — it will need to use viral vectors to make the DNA of humans respond to the drug CNO to increase or decrease neuronal activity.

“By genetic modification, mice are born with this gene in the sensory nerves and, when we give the drug, we only have the activation of those neurons that we want. For humans, we could use viral vectors in what is called gene therapy — you use a virus, it infects the cell and the virus carries the gene into the DNA,” explains Birbrair.

Before conducting the study in humans, the researchers plan to apply the findings to other mammals, such as horses and dogs, to see if the results will be similar to those seen in mice.

In addition, scientists are already carrying out other investigations to test whether sensory neurons would also be useful against breast, prostate and lung cancer, increasing the possibilities for treatment.

“The characteristic of each type of cancer is different and sometimes what works in one has the opposite effect in others”, ponders the professor.