Two-Step Gene Therapy Shows Early Promise in Treating High-Grade Gliomas
Published May 9, 2016
Cancer Cell
Words like “victory” rarely get used when talking about treatments for aggressive high-grade glioma and glioblastoma. The conversation more commonly turns to a sad prognosis focused on how long a child has to live.
However, scientists in our Cancer and Blood Diseases Institute have scored an early-stage research win.
In a study published in May 2016, scientists tested a form of “suicide gene therapy,” an approach that blocks glioma formation by eliminating Olig2-producing tumor cells. In mouse models, the team shut down Olig2, a gene long implicated in forming high-grade gliomas. This changed the tumors' cellular makeup, making them vulnerable to follow-up treatment.
This was the first blow in a one-two punch.
“By inhibiting 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,” says Qing Richard Lu, PhD, lead investigator.
Once altered, the proneural cancer cells behaved more like astrocytes, which produce high levels of epidermal growth factor receptor (EGFR). This protein is a common target for effective chemotherapies against other types of cancer.
Using the drug gefitinib to block EGFR in the mice, Lu and colleagues halted the brain cancers.
Translating this finding into a human clinical trial will require much more study and testing. However, the progress was significant enough to attract a commentary written by Rebecca Ihrie, PhD, and Nalin Leelatian, MD, of Vanderbilt University.
“Intriguingly (the study) provides insight into an experimental paradigm that enables further exploration of how tumor phenotypes may evolve during treatment,” they wrote. The findings represent “exciting steps toward identifying, restricting, and killing elusive cell populations."
