Hebrew U Researchers Discover Promising Treatment for Aggressive Brain Tumors

November 7, 2018

3 min read

Glioblastoma sounds frightening – and it is. This malignancy is the most aggressive cancer that begins inside the brain, and patients who are diagnosed with it usually have only about 11 to 20 months to live. There are rare cases, about 3% to 5% of victims, who survive for five years or more.

Initial symptoms are not specific and may include nausea, headaches, personality changes and even signs of a stroke. But the cancer, which usually begins around age 64, often causes patients to decline quickly, even to unconsciousness. One of the main problems in treating this cancer is that its cells quickly build up a resistance to chemotherapy.

The cause of the tumor, which occurs in three people per 100,000 per year and usually develop in the brain’s white matter, is not known. There are genetic risk factors, such as suffering from neurofibromatosis or Li-Graumeni syndrome. Another risk factor, but unexplained, is having previously undergone radiation therapy.

There is no known way to prevent glioblastoma, and treatment is difficult because the tumor cells are very resistant to conventional therapies and the brain is susceptible to damage from conventional therapy and has a very limited capacity to fix itself.

Another impediment to treatment is that many drugs can’t cross the blood-brain barrier so they could fight the tumor. When there is time for treatment, surgery – followed by chemotherapy and radiation therapy – may be offered. It is unclear whether trying to remove all or simply most of the cancer is better. Yet glioblastomas are usually resistant to conventional chemotherapy, and even after such procedures, the cancer usually comes back.

But now, researchers at the Hebrew University of Jerusalem, Israel have proposed a new treatment for glioblastoma – the type of cancer from which John McCain suffered – that has the potential to improve and lengthen patients’ lives.

Prof. Rotem Karni and his team at the university’s Institute for Medical Research-Israel Canada have just published their promising results in the journal Nucleic Acids Research.

As part of their research, Karni and doctoral student Maxim Mogilevsky designed a molecule that inhibits glioblastoma tumor growth by regulating the proteins it produces. The MKNK2 gene produces two different protein products through a process called “RNA alternative splicing.”  Ironically, these proteins have two opposing functions –MNK2a inhibits cancer growth, while MNK2b supports cancer growth.

The new Hebrew University molecule shifts the splicing of MKNK2 so that production of the tumor-stimulating protein decreases, while production of the tumor-suppressing protein increases. As a result, cancerous tumors decrease or die-off completely.

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

In his study, tumors shrank or died off completely in mice with human glioblastoma tumor cells that were treated with this new molecule. This did not occur in mice that were treated with an inactive molecule.  “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,” added Karni.

A patent for this technology has been registered and granted in the United States and Europe through Yissum, Hebrew University’s research and development company. The research was financed by the

German-Israel Foundation, the Israel Innovation Authority, the Israel Science Foundation, the Israel Cancer Research Fund, the Israel Cancer Association, the Henry & Merilyn Taub Foundation and the Carol Epstein Foundation.

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