Lerner Research Institute News

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NIH Funds Collaborative Study into Mechanisms of Glioblastoma Treatment Resistance

Drs. Yu and Zhao will study the role of a long non-coding RNA called Lucat1 in glioma stem cells in the search for new therapeutics to help treat glioblastoma and overcome treatment resistance.

12/14/2021




Two Department of Cancer Biology researchers have together received a five-year, $2.7 million grant from the National Institute of Neurological Disorders & Stroke to investigate new treatments for glioblastoma. The multi-principal investigator award is to Jennifer Yu, MD, PhD, and Jianjun Zhao, MD, PhD.

Glioblastoma is the most common primary malignant brain tumor. Tumors of this variety are especially prone to treatment resistance, in large part due to the pro-cancer characteristics of a class of cells called glioma stem cells. This includes their ability to self-replicate and renew, especially under harsh conditions like a lack of oxygen (termed hypoxia).

“Glioma stem cells like to reside in the hypoxic regions of glioblastoma tumors,” explained Dr. Yu, who is a practicing radiation oncologist and member of the Center for Cancer Stem Cell Research. “This makes treatment challenging since current therapies, including radiation and chemotherapy drugs, are not able to penetrate as effectively into hypoxic areas.”

This study to identify new treatment targets strategically marries Dr. Yu’s expertise in glioma stem cell biology with Dr. Zhao’s expertise in long non-coding RNAs (lncRNAs).

As implied by the name, non-coding RNA is genetic material that does not encode proteins. These regions of genetic material are still very important, however. For example, some types of non-coding RNA can direct whether genes are turned on or off and some have been implicated in driving disease processes, including certain types of cancer.

“Long non-coding RNAs have been studied in cancer, but relatively little is currently known about their relation to glioma stem cells specifically,” said Dr. Yu. “We do know from preliminary research, however, that expression of a specific lncRNA called Lucat1 is increased 80-100-fold more than normal during hypoxia.”

With this grant, Drs. Yu and Zhao will study Lucat1 signaling to understand if and how the specific lncRNA promotes glioma stem cell properties and cancer progression. “If this new phase of research supports our preliminary findings, therapies that target Lucat1 may hold promise as a combination therapy to complement currently available treatment approaches, like radiation,” said Dr. Zhao.




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