How to Destroy the Power Source of Brain Tumor

An Israeli study has eliminated glioblastoma, the most deadly brain tumors, in mice by identifying and destroying their “power source.” The Tel Aviv University scientists behind the peer-reviewed research are now working on identifying drugs to replicate the effect in humans. They hope to find an existing drug that may work and then repurpose it, which they say could happen within two years if things go smoothly.

The method is basically to “starveglioblastoma tumors by removing their source of energy, said brain immunologist Dr. Lior Mayo, the lead author of the study. He told The Times of Israel that normally, scientists try to attack tumors directly, for example with chemotherapy. “Instead, we decided to ask if there’s anything we can change in the tumor’s environment that could harm it,” he explained.

Astrocytes are brain cells that are so called because they look like stars. Glioblastoma tumors shifts the surrounding astrocytes to an unusually active state. Mayo, and his PhD students Adi Tessler and Rita Perelroizen, wanted to know what the astrocytes do in relation to the tumor. Using genetic modification, he could produce mice with glioblastoma tumors, and then remove all astrocytes from around the tumor.

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An image from the lab of Dr. Lior Mayo showing a glioblastoma tumor in white, surrounded by astrocytes in blue

“We found that when we did this, the tumors vanished and stayed away for as long as we repressed the astrocytes,” Mayo said. “In fact, even when we stopped suppressing the astrocytes, some 85 percent of the mice stayed in remission. However, among the control group, in which all astrocytes remained, all mice died.”

In the study, published in the journal Brain, the scientists suggest “that targeting astrocyte immunometabolic signaling may be useful in treating this uniformly lethal brain tumor.”

Source: https://www.timesofisrael.com/

CRISPR Treatment Destroys Cancer Cells

Researchers at Tel Aviv University (TAU) have demonstrated that the CRISPR/Cas9 system is very effective in treating metastatic cancers, a significant step on the way to finding a cure for cancer. The researchers developed a novel lipid nanoparticle-based delivery system that specifically targets cancer cells and destroys them by genetic manipulation. The system, called CRISPR-LNPs, carries a genetic messenger (messenger RNA), which encodes for the CRISPR enzyme Cas9 that acts as molecular scissors that cut the cells’ DNA.

The revolutionary work was conducted in the laboratory of Prof. Dan Peer at TAU. Dr. Daniel Rosenblum led the research together with Ph.D. student Anna Gutkin and colleagues.

To examine the feasibility of using the technology to treat cancer, Prof. Peer and his team chose two of the deadliest cancers: glioblastoma and metastatic ovarian cancer. Glioblastoma is the most aggressive type of brain cancer, with a life expectancy of 15 months after diagnosis and a five-year survival rate of only 3%. The researchers demonstrated that a single treatment with CRISPR-LNPs doubled the average life expectancy of mice with glioblastoma tumors, improving their overall survival rate by about 30%. Ovarian cancer is a major cause of death among women and the most lethal cancer of the female reproductive system. Most patients are diagnosed at an advanced stage of the disease when metastases have already spread throughout the body. Despite progress in recent years, only a third of the patients survive this disease. Treatment with CRISPR-LNPs in a metastatic ovarian cancer mice model increased their overall survival rate by 80%.

The CRISPR genome editing technology, capable of identifying and altering any genetic segment, has revolutionized our ability to disrupt, repair or even replace genes in a personalized manner,” said Prof. Peer. “Despite its extensive use in research, clinical implementation is still in its infancy because an effective delivery system is needed to safely and accurately deliver the CRISPR to its target cells. The delivery system we developed targets the DNA responsible for the cancer cells’ survival. This is an innovative treatment for aggressive cancers that have no effective treatments today.

This is the first study in the world to prove that the CRISPR genome editing system can be used to treat cancer effectively in a living animal,” explained Prof. Peer. “It must be emphasized that this is not chemotherapy. There are no side effects, and a cancer cell treated in this way will never become active again. The molecular scissors of Cas9 cut the cancer cell’s DNA, thereby neutralizing it and permanently preventing replication.”

The results of the groundbreaking study were published in November 2020 in Science Advances.

Source: https://english.tau.ac.il/
AND
 https://www.eurekalert.org/