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May 2014—When Henry Brem finished his neurosurgery training in 1984, the U.S. Food and Drug Administration hadn’t approved a new therapy for the deadliest type of brain cancer in 20 years. The treatments being tried for glioblastoma were showing no benefit. As late as 10 years ago, average patient survival time after a grueling course of surgery, chemotherapy and radiation was just 10 months.
In the last decade, physicians and researchers have worked hard to improve treatments for brain cancer patients, finding new ways to deliver drugs directly to the brain and mitigate some of the side effects. Researchers have found new targets to attack with new compounds. They are working on immune therapy, discovering a way to program the body’s immune system to attack cancer cells instead of allowing them to grow unchecked. Average patient survival from glioblastoma is now 20 months.
“On the one hand, we have done a tremendous amount of work and have been able to double life expectancy,” says Brem, the Harvey Cushing Professor of Neurosurgery at the Johns Hopkins University School of Medicine and the director of the Department of Neurosurgery. “But this disease is still terrible. It hits people at the prime of their lives, and they survive less than two years. It’s better than it was but far from where we want to be.”
Brem has been heavily involved in the development of the Gliadel wafer, a biodegradable polymer loaded with a chemotherapy agent that is used to treat gliomas, of which glioblastoma is one type. After surgical removal of the tumor, the wafers are placed in the spot where the tumor was to destroy the remaining cancer cells.
This is a local drug delivery technique that eliminates the side effects of systemic chemotherapy such as fatigue and hair loss.
Brem says the next step is to create a microchip that would allow controlled release of the chemo drug over a longer period of time. A similar technique has been tested with parathyroid hormone in patients who need it, and the drug is released over time in response to commands given via cellphone. A brain cancer microchip is in the pipeline, Brem says.
Among the treatments being looked at by Johns Hopkins and other researchers are experimental drugs aimed at blocking proteins called PD-1 and PD-L1, which shield tumors from attack by the immune system. Another approach involves using a drug called 5-azacytidine to target a mutation in the IDH1 gene, which produces an enzyme that regulates cell metabolism. The targeted mutation found in some brain cancers forces the IDH1 gene to increase production of a flawed version of the enzyme, which ultimately causes groups of atoms called methyl groups to latch onto the DNA strand. The drug 5-azacytidine strips off the methyl groups and, in mice, halted cancer growth and left no detectable trace of the disease.
“We try to choose the most promising treatments with the widest application,” Brem says. “These improvements are only the beginning. We’re changing the field and the outcomes of these patients. While the changes have so far been small, there is much more in the development pipeline than there ever was before.”
The Hunt for a Brain Tumor Vaccine