A new study from Tel Aviv University has effectively eradicated glioblastoma, a highly lethal form of brain cancer.
The researchers achieved this ground-breaking discovery by using a method they had previously developed whilst researching two critical mechanisms in the brain. These mechanisms support tumour growth and survival. One protects cancer cells from the immune system, and the other supplies energy to the tumour, allowing rapid growth.
The team found that both these mechanisms are controlled by brain cells called astrocytes. In the absence of astrocytes, the tumour cells will die and be permanently eradicated from the brain.
The findings are published in the scientific journal Brain.
Previous glioblastoma treatments have been ineffective
“Glioblastoma is an extremely aggressive and invasive brain cancer, for which there exists no known effective treatment. The tumour cells are highly resistant to all known therapies, and, sadly, patient life expectancy has not increased significantly in the last 50 years. Our findings provide a promising basis for the development of effective medications for treating glioblastoma and other types of brain tumours,” said Dr Lior Mayo of the Shmunis School of Biomedicine and Cancer Research.
The researchers approached the challenge of glioblastoma from a new angle. Rather than focusing directly on the tumour, the team focused on the tumour’s supportive microenvironment. The team specifically studied the astrocytes. Previous research from Tel Aviv University has found astrocyte functions that can alleviate or aggravate various brain diseases.
“Under the microscope, we found that activated astrocytes surrounded glioblastoma tumours. Based on this observation, we set out to investigate the role of astrocytes in glioblastoma tumour growth,” explained Dr Mayo.
Using an animal model, the team could eliminate active astrocytes around the tumour. It was found that in the presence of astrocytes, the cancer killed all animals with tumours within four to five weeks.
Positive results found after experimentation
When applying the unique method of specifically eradicating the astrocytes near the tumour, the researchers observed a dramatic outcome; the tumour had disappeared within a matter of days. All the animals that underwent this treatment survived, even after the treatment was discontinued.
“In the absence of astrocytes, the tumour quickly disappeared, and in most cases, there was no relapse – indicating that the astrocytes are essential to tumour progression and survival. Therefore, we investigated the underlying mechanisms: How do astrocytes transform from cells that support normal brain activity into cells that support malignant tumour growth?” said Dr Mayo.
To answer these questions, the researchers compared the gene expression of astrocytes isolated from healthy brains against those from glioblastoma tumours. Two main differences were observed – the first change was in the immune system’s response to the glioblastoma.
“The tumour mass includes up to 40% immune cells – mostly macrophages recruited from the blood or from the brain itself. Furthermore, astrocytes can send signals that summon immune cells to places in the brain that need protection. In this study, we found that astrocytes continue to fulfill this role in the presence of tumours. Specifically, we found that the astrocytes change the ability of recruited immune cells to attack the tumour both directly and indirectly” Dr Mayo said.
The second difference was the way in which the astrocytes support glioblastoma, by modulating their access to energy via the production and transfer of cholesterol to the tumour cells.
“The malignant glioblastoma cells divide rapidly, a process that demands a great deal of energy. With access to energy sources in the blood barred by the blood-brain barrier, they must obtain this energy from the cholesterol produced in the brain itself. We discovered that the astrocytes surrounding the tumour increase the production of cholesterol and supply it to the cancer cells,” explained Dr Mayo.
“Our findings suggest that, at least in the specific case of glioblastoma, the blood-brain barrier may be beneficial to future treatments, as it generates a unique vulnerability – the tumour’s dependence on brain-produced cholesterol. We think this weakness can translate into a unique therapeutic opportunity.”