New treatment ‘starve’ aggressive brain tumors in mice

Researchers at Tel Aviv University Discover A way to ‘starve’ glioblastoma tumors in the brains of mice–suggesting a new way to finally fight deadly cancer in humans.

the challenge: glioblastoma It is a rare but aggressive type of brain cancer that is almost always fatal in adults – the median survival time is only 12-18 monthsOnly 5% of patients live more than five years after diagnosis.

Glioblastoma does not respond to known cancer treatments, and The blood-brain barrier It makes developing new software a challenge. While the barrier is necessary to prevent microorganisms in the bloodstream from reaching the brain, it also prevents drugs from entering brain tumors.

Only 5% of people with glioblastoma live more than five years after diagnosis.

The idea: When the Tel Aviv team looked at glioblastoma tumors under a microscope, they noticed that they were surrounded by active “astrocytes,” a type of star-shaped brain cell that is not per se cancerous but is linked to the development of many brain diseases.

This inspired them to take a closer look at the role stellate cells play in the growth of glioblastoma tumors with the hope that it could lead to a new treatment angle.

Eyes on astrocytes: The team used a unique method to remove all of the active stellate cells around the mice’s glioblastoma tumors – and caused their cancer to disappear within days.

All treated animals survived for the duration of the study, while all untreated animals died within 4-5 weeks. Brain tumors kept disappearing for as long as the treatment continued, but even after it was stopped, 85% of treated animals She remained free of cancer.

“Astrocytes convince immune cells to ‘change sides’ and support the tumor rather than attack it.”

Lior May

Next, the team compared the gene expression of astrocytes in healthy brains to those found near glioblastoma tumors, and found two key differences.

The first is that astrocytes close to tumors use their ability to summon brain immune cells helps Cancer instead of fighting it.

“[O]Once the invoked immune cells reach the tumor, the astrocytes “convince” them to “switch sides” and support the tumor rather than attacking it,” said corresponding author Leor Mayo.

A second difference was that astrocytes close to tumors increase their production of cholesterol – which is normally used to power other brain cells – and take it directly to glioblastoma tumors.

“With access to energy sources in the blood blocked by the blood-brain barrier, [the glioblastoma cells] This energy must be obtained from cholesterol produced in the brain itself,” Mayo said.

The team then engineered the astrocytes to stop production of a protein needed to transport cholesterol. When these astrocytes were tested in animal models and samples from human patients, glioblastoma tumors were “starved” of energy and died within a few days.

Leap for humans: So far, all of the team’s research has been done on animals or in lab samples, so we don’t know if their results will translate to patients — but their analysis of hundreds of glioblastoma patients gives cause for hope.

“For each patient, we examined the expression levels of genes that either neutralize the immune response or provide the tumor with a cholesterol-dependent energy supply,” the researchers wrote.

They continued, “We found that patients with poor expression of these specific genes lived longer, supporting the concept that specific genes and processes are important for the survival of glioblastoma patients.”

“In the specific case of glioblastoma, the blood-brain barrier may be useful for future therapies.”

Lior May

I look ahead: More research is needed before the team can try to translate its findings into a treatment for people, but their study is an encouraging sign that a new type of cancer treatment could be on the horizon.

“Our findings, at least in the case of glioblastoma, suggest that the blood-brain barrier may be useful for future therapies, because it generates a unique weakness — the tumor’s dependence on cholesterol produced by the brain,” Mayo said.

“We believe this weakness can translate into a unique treatment opportunity.”

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