Promising therapeutic target for meningioma brain tumors

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A specific protein has been found in nearly 100% of high-grade meningiomas, which is the most common form of brain tumor. This finding suggests a new target for therapies for a cancer that does not respond to current chemotherapy.

Importantly, the investigators stated that the protein, NY-ESO-1, is already at the center of a clinical trial underway at the National Cancer Institute. That trial is designed to activate the immune systems of patients with other types of tumors that express the protein, training the body to attack the cancer and eradicate it.

"Typically there is a lag time before a laboratory finding like this leads to a clear path forward to help patients. But in this case, since there is already a clinical trial underway, we have a chance of helping people sooner rather than later," said senior author Gregory J. Riggins, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland. The study was study published online in Cancer Immunology Research (2013; doi: 10.1158/2326-6066.CIR-13-0029).

In the NCI trial, NY-ESO-1 is found in a much smaller percentage of tumors than Riggins and his team found in high-grade meningioma, suggesting that for the brain cancer, the target would be potentially more significant.

Most low-grade meningiomas located in easy-to-reach locations can be treated successfully with surgery and radiation. But more atypical, higher-grade tumors are much more difficult to eradicate and are deadlier.

The research team set out to find cancer antigens in meningioma. Cancer antigens are proteins expressed in tumors but not in healthy cells, making them good targets for chemical or immune system attack.

The Johns Hopkins researchers took tissue from 18 different meningioma samples, removed the genetic material and protein, and checked at what levels 37 different genes were turned on. The gene that is the blueprint for the NY-ESO-1 protein was turned on more frequently than any other, in five of the 18 patient samples.

Then they analyzed NY-ESO-1 expression in a larger group of 110 meningioma tissue samples. They found NY-ESO-1 in 108 of them. The more expression in the sample, they also determined, the higher the tumor grade. The higher levels of NY-ESO-1 expressed also correlated with significantly lower disease-free and overall survival rates in the patients they came from.

Riggins called the fact that the NCI trial could now include meningioma patients a "stroke of luck."

"If that therapy did not exist, there would be a lot of work that would have to be done to convince people to pursue this," Riggins said. "Our goal is to get something that works to the patients. This puts us well on our way."
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