Experimental therapy halts treatment-resistant Brain Tumors

A multi-institutional team led by researchers at Cincinnati Children's Hospital Medical Center publishes their results on May 9. Testing a multi-step therapeutic strategy, the scientists found a way to use a gene therapy to shut down a gene long-implicated in the formation of high-grade gliomas called Olig2. The protein encoded by Olig2 is expressed in the majority of gliomas. Removing the Olig2 gene halts tumor growth, while elimination of Olig2-producing cells blocks tumor formation.
"We find that elimination of dividing Olig2-expressing cells blocks initiation and progression of glioma in animal models and further show that Olig2 is the molecular arbiter of genetic adaptability that makes high-grade gliomas aggressive and treatment resistant," said Qing Richard Lu, PhD, lead investigator and scientific director of the Brain Tumor Center at Cincinnati Children's. "By finding a way to inhibit Olig2 in tumor forming cells, we were able to change the tumor cells' makeup and sensitize them to targeted molecular treatment. This suggests a proof of principle for stratified therapy in distinct subtypes of malignant gliomas." The current study may apply to high-grade brain gliomas and a fatal brainstem tumor called DIPG (Diffused Intrinsic Pontine Glioma), which expresses Olig2 and is inoperable because of its location in a brain region controlling vital functions. Even if these cancers do initially respond to a specific targeted treatment, they adapt by finding genetic/molecular workarounds, evade treatment and continue growing. Researchers caution the experimental therapeutic approach they describe requires extensive additional research and remains years away from possible clinical testing. Still, Dr. Lu said the data are a significant research breakthrough. The current study finds a potential chink in the molecular armor of these stubborn cancers.