Biotechnology

A major advance when scientists make brain tumors self-destruct

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Researchers at the University of Gothenburg in Sweden, in collaboration with French colleagues, have successfully developed a method capable of killing the aggressive brain tumor glioblastoma. By blocking certain functions in cells with anchored molecules, researchers cause cancer to die from stress.

Cancer cells, especially those that form aggressive tumors, in one way or another get out of control and lead very stressful lives. To deal with this stress, cancer cells hijack the mechanisms that healthy cells use to regulate protein production and process the excess proteins they make. Without this hijacked mechanism, cancer cells would die.

“We have now successfully stopped this hijacking by introducing specially developed molecules into cells that inhibit one of these hijacked adaptive mechanisms in cancer cells. This causes cancer to self-destruct,” said Leif Eriksson, professor of physical chemistry at the University of Gothenburg.

Swedish-French collaboration

Eriksson’s group has been working with a research group at INSERM in Rennes, France. Using supercomputers and advanced simulations, the researchers developed a version of the molecule that can also cross the blood-brain barrier that protects brain tissue. They presented their findings in a journal iScience.

This breakthrough applies to glioblastoma brain tumors. It makes up about 45% of all brain tumors and about 400 Swedes are diagnosed with glioblastoma each year. For the EU as a whole, there are 19,000 cases annually. Currently, the prognosis of malignant glioblastoma is very poor. Only a few percent survive five years after diagnosis and treatment.

“Currently, cancer treatment consists of surgery, radiation and chemotherapy. Unfortunately, all cancer cells do not die and the tumor returns. Once the cancer has recurred, the tumor cells often spread and develop resistance,” says Eriksson.

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The researchers’ Z4P molecule inhibits one of the mechanisms that regulate protein production in cancer cells. This inhibition causes cancer cells to die. Three images show tumor spread after 20 days of treatment in mice. Control: Tumors are not treated. TMZ: Follow-up care with chemotherapy only. Combo: Combination treatment with chemotherapy and a Z4P inhibitor. Molecular drawings: X. Guillory, photos from animal studies: D. Pelizzari-Raymundo.

Studying other cancers

Studies with new methods have shown very promising results. The researchers saw that a combination treatment with the new substance and chemotherapy was enough to completely kill the tumor while preventing its recurrence. Because the tumor was suppressed to death, all the cancer cells disappeared, and in animal experiments with mice no cancer recurred after 200 days. In a comparative trial with chemotherapy alone, brain tumors recurred after 100 days and grew rapidly.

“This is the first clear result with a brain tumor that could lead to a treatment that completely avoids surgery and radiation. We have also begun to study the use of our substances in other forms of aggressive tumors such as pancreatic cancer, triple-negative breast cancer and certain lever cancers,” said Eriksson.

There are other types of brain tumors that develop differently from glioblastomas. This new method does not work with this type of cancer.

There are no side effects for this new brain tumor treatment

Current treatments for brain tumors often have severe side effects. With this new treatment, researchers have not seen any side effects from the substance. The treated animals maintained their weight, had no noticeable changes in behavior and no signs of liver impact. While more in-depth studies are needed, extensive cell tests have shown that the substance is not toxic to healthy cells even at very high doses.

Research on this molecule will now continue. Much remains to be done, such as optimizing treatment procedures and additional animal trials. But Leif Eriksson hopes and believes that it will have to go relatively quickly to get the drug into clinical care.

“It really depends on whether the funds come in which allows taking the different steps as smoothly as possible. If I’m optimistic, it might take five years. That’s a short timeframe, but at the same time glioblastomas are almost 100% fatal, so any improvement in medical care is a huge advance,” concluded Eriksson.

The news comes a day after Rznomics was given FDA approval for a glioblastoma treatment trial.

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