A Breakthrough in Fighting Brain Cancer

A promising new drug against a particularly deadly form of brain cancer is being developed in the lab of Rotem Karni at the Institute for Medical Research Israel-Canada of the Hebrew University-Hadassah Medical School in Yerushalayim.

Rotem’s postdoctoral fellow, biochemist Regina Golan-Gerstl, had previously identified a genetic protein called splicing factor hnRNP A2/B1, involved in the spread of glioblastoma, the most common and aggressive type of brain cancer in adults.

Glioblastoma tumors are nearly impossible to remove with surgery, and rarely respond completely to chemotherapy or radiation. Only about 10 percent of glioblastoma patients live five years or longer after diagnosis. The median survival rate, even with medical intervention, is just over a year.

We developed some molecules that can inhibit production of this gene, says Karni.

The gene hnRNP A2/B1 is a naturally occurring substance in the human body. But the Israeli scientists found that in the very early stages of cancer, its production goes into overdrive and enables the cancerous tumor to grow and spread.

Golan-Gerstl and her team proved that reducing the amount of hnRNP A2/B1 in lab mice before injecting glioblastoma cells made a dramatic difference in the ability of the cells to proliferate. This group of mice developed only small tumors or no tumors at all, while untreated mice developed large brain tumors when injected with glioblastoma cells.

Karni says they have since shown that the same therapeutic effect takes place in human glioblastoma cells where hnRNP A2/B1 is suppressed, and they are currently studying the technique in further animal models.

In collaboration with physicians at Hadassah-Ein Karem Medical Center, Karni and his lab are testing the diagnostic value of this gene in brain-cancer patients. He explains that looking at the level of hnRNP A2/B1 can serve as an unprecedented marker to predict survival of people with glioblastoma tumors, and could help doctors formulate the most effective treatment plan for each patient.

A medication to suppress the gene is the next obvious step. If we inhibit it, we can really reverse the cancer cells back to normal, Karni says.