Glioblastoma: Experimental Treatment Eradicates Tumors in Animal Model

This week SciTech Daily published news of the successful eradication of a heretofore incurable form of brain cancer. The research was conducted at Israel’s Tel Aviv University in collaboration with the NIH in the United States.

The researchers discovered two mechanisms. One protects cancer cells from the body’s immune system. The second mechanism promotes energy that is required for the tumor to grow rapidly. The team identified astrocytes (brain cells) that control both processes. When these astrocytes are missing, tumor cells die and are subsequently eliminated.

The lead researcher was Dr. Rita Perelroizen under the supervision of Lior Mayo, M.D. of Shmunis School in Tel Aviv. The journal Brain published the study adding scientific commentary.

About The Study

Tumor cells in glioblastoma are resistant to every known therapy. Life expectancy for glioblastoma patients has hardly increased over the past fifty years. The new findings represent the solid basis that is needed to develop medications to treat not only glioblastoma but other forms of brain tumor.
Dr. Mayo explained that the team began the study using a new approach. Rather than targeting the tumor, the team zeroed in on a supportive microenvironment. In other words, the target became the tissue surrounding the tumor cells. In this case, it was the astrocytes affecting brain function. Astrocytes were first identified almost two hundred years ago. Their name evolved from their likeness to stars.

Dr. Mayo further explained that current research identified certain astrocyte functions that have either positive or negative effects on the disease of the brain. When examined under a microscope the team found astrocytes surrounding glioblastoma tumors. This led the researchers to investigate astrocytes’ role in the growth of these tumors.

Animal models were the recipients of a unique method that removed the astrocytes surrounding the tumor. They found that where active astrocytes were present, within four to five weeks cancer killed every animal that had glioblastoma tumors.

A Startling Discovery

Once the astrocytes surrounding the tumor were eradicated, the cancer was eliminated within days. All animals that received treatment remained alive, including in the period of treatment discontinuance.
Now the question is how do the astrocytes support normal activity in the brain as well as provide support for the growth of malignant tumors? The researchers set out to find the answers. They compared astrocytes taken from healthy brains to astrocytes taken from glioblastomas.

The answers were in the changes they found during astrocytes’ exposure to glioblastoma. One change involved the immune response to the disease. According to Dr. Mayo, immune cells represent about forty percent of each tumor mass which are mostly macrophages that circulate and remove dead cells.
Dr. Mayo further described how the immune cells are summoned by astrocytes to areas of the brain needing protection. Once the immune cells respond and are at the site of the tumor, the astrocytes become the antagonists and “recruit” the immune cells to support the tumor rather than attacking it. Thus the cancer becomes more aggressive.

One other factor in astrocyte’s support of glioblastoma is through transferring cholesterol to tumor cells which then divide rapidly. This procedure requires a high level of energy. The blood-brain barrier prevents such access. Therefore, energy must be obtained directly from cholesterol that is produced by the brain and is transmitted to various brain cells and neurons.

Starving the Tumor

In analyzing the astrocytes that surround a tumor, the researchers found that these astrocytes increase the production of cholesterol which is then supplied to cancer cells. Since the tumors depend on this specific cholesterol for energy, removing the supply of cholesterol starves the tumor.

Another method used by the researchers prevents the astrocytes from expressing a cholesterol-transporting protein (ABCA1). This blocks the release of cholesterol into the tumors. The researchers released news of their remarkable results that killed the tumors in a matter of days.
To better confirm the aforementioned results, hundreds of databases of patients diagnosed with glioblastoma were correlated with the new findings.

In conclusion, Dr. Mayo stated that their new challenge is to develop drugs which target the astrocytes that promote the growth of tumors. He hopes that their new findings will become the basis for effective treatments to cure glioblastoma and other forms of brain tumors.