New Research May Lead to a Cure for an Aggressive Form of Brain Cancer

A very aggressive form of brain cancer may have met its match according to two research teams from two different Israeli universities.

In December 2018, researchers at Sheba Medical Center Tel Hashomer, affiliated with Tel Aviv University announced that they might have found a cure for patients with Glioblastoma, a very aggressive brain cancer. Just a month earlier, researchers at Hebrew University in Jerusalem found a new radically different treatment for the same disease.

Glioblastoma (GBM) is the most common and most aggressive brain cancer. GBM occurs in two-to-three per 100,000 adults per year, or roughly 240,000 new cases a year worldwide. This is the type of cancer that struck Arizona Senator John McCain who died last year.

There is no known cure for this aggressive cancer. Treatment today consists of surgical approaches in combination with radiation and chemotherapy. Patients rarely survive over two years according to the Sheba Medical Center researchers whose study was published in of Frontiers in Neurology magazine.

That’s why Israeli neuroscientists Dr. Efrat Shavit-Stein and Professor Yoav Chapman, who have been working on the treatment at the Joseph Sagol Neuroscience Center, Sheba Medical Center had to look for an innovative new approach.

Recent research found that thrombin (a coagulation factor that is secreted from tumor cells) and PAR1 (a protease-activated receptor) are part of the pathology of GBM tumors. Based on this chemical structure, the neuroscientists created a drug called SIXAC, an amino-acid based compound that inhibits PAR1 according to the researchers.

In animal testing, direct injections into the brain tumors resulted in reducing the tumors and had a life-extending result according to the researchers. In 10 percent of the test subjects, the drug actually cured them of the disease.

“Our results suggest that SIXAC will be a very interesting compound in both studying and modulating PAR1 in GBM,” the researchers said in their study. “We hope that future treatment with SIXAC can be an add-on therapy to the accepted radio-chemotherapy and improve survival in GBM patients, as well as potentially their quality of life by reducing tumor-associated edema.

“The drug has shown outstanding results in an animal model of the tumor and we hope to be able to use it soon in human subjects with this terrible disease,” Prof. Chapman said in a statement from Sheba Medical Center.

Research in GBMs was also conducted at Hebrew University, and a new treatment was designed that shows great promise according to a report published in the journal Nucleic Acids Research. The research team headed by Prof. Rotem Karni and PhD student Maxim Mogilevsky at Hebrew University’s Institute for Medical Research-Israel Canada took a completely different approach from the Sheba Medical Center team.

The researchers looked to regulate BBM tumor growth by regulating the protein it produces and they designed a molecule that inhibits growth. The MKNK2 gene produces two different protein products through a process called “RNA alternative splicing.” One inhibits cancer growth and the other supports cancer growth. The researchers manipulated this split so that the tumor-stimulating protein dies off and the tumor-suppressing protein increases according to the study.

“Not only can this breakthrough molecule kill tumor cells on its own, it has the power to help former chemotherapy-resistant cells become chemotherapy-sensitive once again,” Karni told Israel21.

The animals used in the study were treated with the new molecule and the tumors shrank or the cancerous tumors died entirely.

“Our research presents a novel approach for glioblastoma treatment. In the future, we’ll be able to tailor treatments for patients based on the amount of cancer-inhibiting proteins that their tumors produce,” Karni said.

Both of these new approaches show great promise. If human trials prove equally successful, these two new treatment approaches could prolong the lives or completely cure the people who suffer from this aggressive form of brain cancer. That would be very welcome news.