2023-07-24 08:06:42
Neurons and nerves power tumors with a poor prognosis, including those of the brain and pancreas. The process could be reversed with drugs already approved for neurological and circulatory diseases.
American neurologist Michelle Monje has spent years seeing a surprising pattern in some of her patients with glioblastoma, the deadliest type of brain cancer. After the primary tumor is removed, the cancer recurs after a while; but she does not do it in any part of the brain, but in the area that the patients used the most for their work. In the case of a classical dancer, she reappeared in the area of the cerebellum that controls balance. In one writer, she regrew multiple times in the area of the cerebral cortex where language resides.
“It is a pattern recognized by many neuropsychiatrists,” says Monje. “I wonder if the fact that these people have greater development and plasticity in these areas of the brain made them have a greater risk of suffering from this type of tumor”, highlights the researcher from Stanford University (United States). The scientist she is one of the promoters of cancer neuroscience, a new discipline that tries to unravel the connection between brain activity and cancer. Neural activity promotes the growth of gliomas, the most common brain tumor.
In a recent study, Monje and other neurologists looked at which areas of the brain are activated in patients with glioblastomas when they perform simple cognitive activities, such as looking at the picture of an umbrella and saying the word umbrella.
When the patients responded, not only the Broca area that controls language was activated, but also other brain areas invaded by the tumor. The cancer had reorganized the brain’s speech circuits, based on the synapses between neurons, to connect to them. Electrical currents generated during these cognitive tasks reach the tumor and promote its growth. The more the affected areas lit up, the worse the prognosis of the patients, who also gradually lost their ability to speak. It is likely that the neuronal overstimulation caused by the tumors explains why many patients suffer epileptic seizures and cognitive problems.
Brain tumors, gliomas and glioblastomas represent around 2% of all tumors diagnosed each year. Despite their low incidence, they represent a great challenge for medicine, as they respond very poorly to treatments. Gliomas represent 15% of all childhood tumors and the leading cause of death from cancer.
The interaction between the nervous system and cancer extends to other organs through the nervous ramifications that go from the brain to the rest of the body and whose length reaches 150,000 kilometers.
Another example occurs in the optic nerve, which carries visual signals from the eyes to the brain.
Malignant cells advance along the nerves and receive key molecules for their growth from them. Tumors with more nerve branches have a poorer prognosis in the prostate, stomach, or pancreas, according to animal studies and analyzes of patient samples. In some cases, malignant cells from a primary breast tumor can migrate to the brain, nestle in it, connect to neurons, and metastasize much more deadly than the primary tumor.
The interaction between the nervous system and cancer is complex and different in each organ. In the stomach, acetylcholine, a neurotransmitter, promotes the expansion of tumor cells, but in the pancreas it has just the opposite effect and slows tumor progression.
The connection between the nervous system and cancer is seen in many other organs. A surprising case connects the nervous system, the immune system and cancer. nuno dominguez
This role of the nervous system in cancer has been ignored for a long time. In 1899, the Spanish physician and Nobel Prize winner for Medicine Santiago Ramón y Cajal was the first to describe a growth pattern of nervous tissue in which glia, a type of nerve cell, grew around neurons, as if they were their scaffolding.
At the beginning of the last century, the German pathologist Hans-Joachim Scherer observed the same structures in samples from patients with brain cancer: tumor cells grew around neurons and it was very difficult to determine where the tumor ended and healthy brain tissue began.
This research was practically at a standstill until 10 years ago, when physician and researcher Paul Frenette, from the Albert Einstein School of Medicine (United States), presented the first tests in animals and patient samples that the more nerve endings prostate tumors have, the more aggressive they are and the worse they respond to treatment.
Since then, similar connections have been observed in other organs and this new field of research has exploded, sums up Frank Winkler, a neuro-oncologist at Heidelberg University Hospital (Germany) and leader of research in this field in Europe. “We now know that tumor cells form connected networks and communicate with each other just like neurons do,” he explains. “Many of the biochemical processes that we observe are the same that take place in an embryo to form all the organs of the body. The tumor behaves like any other organ. It doesn’t invent new mechanisms to grow, but takes over the ones that are already invented”, adds Winkler. His team has perfected a new microscopy technique to study the formation of tumors, their communication with the rest of the brain cells, their progression and reappearance in live animals and in real time. These data are crossed with those observed in patients with brain tumors to try to better understand this new dimension of cancer.
Neuroscientist Manuel Valiente, from the National Cancer Research Center, believes that cancer neuroscience can clarify not only the role of the nervous system in driving primary tumors, but also brain metastases, which are 10 times more frequent than glioblastoma. In addition, “investigating these connections could shed light on why brain tumors cause cognitive damage in 44% of patients, and perhaps help avoid them so their minds aren’t affected as much while they’re on treatment,” he explains.
One of the explanations for why this field is still taking off is that traditionally cancer research teams did not know how to analyze nervous tissue, nor neural activity, based on a complicated interaction between small electrical currents and the production of biochemical compounds. Physicist and neuroscientist Liset Menéndez de la Prida, head of the neural circuits laboratory at the Cajal Institute, is a specialist in this type of analysis. Together with Valiente, she participates in a European project funded with 3.5 million euros to develop new photonic tools to measure the electrical and biochemical activity of cancer cells within the brain. “We are seeing a whole paradigm shift and the birth of a new field”, highlights the scientist.
Manuel Sepúlveda, an oncologist at Hospital 12 de Octubre in Madrid, explains that brain tumors, both glioblastomas, the most aggressive, and low-grade gliomas, originate from mutations in glial cells, another type of nerve cell. “The nervous system by itself would not initiate it, but it does encourage it and promote its growth,” he points out. “We are seeing that there is a new way to study this type of tumors, although the importance of this interaction with the nervous system has yet to be determined and whether it can be stopped with drugs”, he details. Sepúlveda has recently participated in a clinical trial that has shown how a drug directed at specific mutations in gliomas can significantly delay the recurrence of cancer after surgery. There are patients who have not suffered relapses or epileptic seizures for six years.
There are drugs already approved to treat mental, circulatory and neurological diseases that affect some of the mechanisms observed and that could interfere with the development of tumors, both in the brain and in other organs. Trials are already underway in patients with perampanel, an anti-seizure drug that blocks glutamate-mediated communication between tumors and neurons. Another trial in patients is studying the effects of meclofenamate, a pain medication, in blocking communication between tumor cells in patients with glioblastoma.
“A whole new field of therapeutic interventions in tumors with a very poor prognosis is opening up,” highlights Michelle Monje, who believes that intervening in the nervous system could become a new pillar of oncology in a similar way to what has happened with immunotherapy, which affects the immune system and has curable tumors that were previously a death sentence. “Blocking the communication between the tumor and the nervous system may not be enough to eliminate it, but I think it will be absolutely necessary to do so,” she concludes.
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