Scientists report finding a potentially promising treatment target for aggressive and deadly high-grade brain cancers like glioblastoma. But they also say the current lack of a drug that hits the molecular target keeps it from being advanced for testing as a therapeutic strategy for patients with few treatment options.

Publishing their data online June 18 in Nature Cell Biology, researchers at the Cincinnati Children's Cancer and Blood Diseases Institute point to a protein that helps regulate cell metabolism called AMPK (AMP-activated protein kinase). Their data suggest AMPK is a key driver of the mostly untreatable brain cancers, and blocking it may produce therapeutic benefit for very ill patients.

But the finding also challenges the scientific status quo regarding AMPK. This is because current research literature characterizes it as a cancer suppressor, according to the study’s senior investigators, Biplab Dasgupta, PhD, and first author Rishi Raj Chhipa, PhD—both scientists in the Division of Oncology at Cincinnati Children’s.

“AMPK is considered to play a suppressive role in cancer because it inhibits cancer-promoting enzymes like mammalian target of rapamycin (mTOR) and acetyl Co-A carboxylase (ACC),” Dasgupta said. “Our study uses analysis of The Cancer Genome Atlas to show that AMPK proteins are highly expressed in lethal human glioblastoma, that inhibiting AMPK by genetic means shrinks brain tumors and prolongs survival in mice. It also shows that deleting AMPK from the whole body of adult mice is safe for the animals.”

The Cancer Genome Atlas is a collaboration between the National Cancer Institute (NCI) and the National Human Genome Research Institute that has generated comprehensive, multidimensional maps of the key genomic changes in 33 types of cancer. According to the NCI, the database is publicly available, making it helpful to the cancer research community to improve the prevention, diagnosis, and treatment of cancer.

Although data in the current study support the feasibility of using pharmacological inhibitors of AMPK to treat glioblastoma, years of additional research are needed before it will be known if the findings are clinically relevant. “We are hopeful our studies will encourage pharmaceutical companies to screen for AMPK inhibitors,” Dasgupta said.

Investigators are planning the next research phases that will be needed to translate the findings to patient care. Dasgupta explained that fostering research collaborations with companies or other institutions with expertise in developing pharmaceutical compounds would help advance the potential therapeutic strategy.