Scientists find potential therapy to suppress deadly brain cancer genes

Nearly 16,000 new cases of glioblastoma multiforme (GBM), a deadly and incurable brain tumor, are reported each year in the United States, and the median survival rate is only 14 to 16 months.

While chemotherapy drugs can help damage DNA and halt the reproduction of these cancer cells, researchers at Northwestern University have discovered a method that goes a step further and stops the source that creates those cells.

Scientists observed that, in mice, the molecule miR-182 suppressed tumors and reduced the expression of multiple oncogenes that cause cancer to progress. The molecule works by blocking cancer cell death in response to radiation and chemo, according to a news release. MiR-182  is a microRNA that can bind to hundreds of genes to reduce their protein expression in cells. Human gliobastoma multiforme patients with greater levels of miR-182 also have higher survival rates than those with lower levels, the study authors found.

In their research, published Thursday in the journal Genes and Development, the authors used a nanostructure called spherical nucleic acids (SNAs) to transport miR-182 across the blood-brain barrier and target multiple oncogenes, leading to cancer cell death and preventing their expansion.

SNAs, which are comprised of DNA and RNA located around a nanoparticle center, are “a very promising platform to silence the particular genes that drive or contribute to cancer progression in individual patients,” senior study author Alexander Stegh, assistant neurology and medicine professor at the Northwestern Feinberg School of Medicine, said in the news release. Study co-author Chad Mirkin, a medicine professor at Northwestern, invented SNAs, a technique that prevents toxicity or activation of the immune system.

“Our approach to gene silencing has not been demonstrated before in such a powerful way for the treatment of brain cancers,” Stegh said. “These particles, microRNA-based SNAs, could also potentially be used for gene silencing in other cancers and diseases of genetic origin.”

The study authors said further research will involve testing miR-182 with the nanoparticle delivery in human patients. But before that becomes an option for glioblastoma multiforme patients, Stegh and his colleagues plan to analyze treatments that combine miR-182 and chemotherapy in mice.