Starving Cancer Cells of Cholesterol Could Help Treat Glioblastomas
Research suggests that blocking cancer cells’ access to cholesterol may offer a new strategy for treating glioblastoma, the most common and deadly form of brain cancer, and perhaps other malignancies.
This treatment could be appropriate for tumors with a hyperactive PI3K signaling pathway, which accounts for up to 90 percent of glioblastoma cases.
Investigators at Ohio State and UCLA’s Jonsson Comprehensive Cancer Center who led the study discovered that the hyperactive signaling pathway is linked to cholesterol metabolism, and that inhibiting this pathway leads to the death of glioblastoma cells in an animal model.
“Our research shows that the tumor cells depend on large amounts of cholesterol for growth and survival, and that pharmacologically depriving tumor cells of cholesterol may offer a strategy for treating glioblastoma,” says first author Deliang Guo, PhD, of the Department of Radiation Oncology at Ohio State.
“This study uncovers a mechanism that links a common oncogene with altered cell metabolism, and it potentially offers a strategy for blocking that mechanism and causing specific tumor-cell death without significant toxicity,” says principal investigator Paul Mischel, MD, professor of Pathology at UCLA and adjunct professor of Radiation Oncology at Ohio State. “Our findings suggest that developing drugs to target this pathway may lead to more effective treatments for patients with this cancer.”
Glioblastomas are difficult to surgically remove because malignant cells invade surrounding brain tissue. Also, genetic differences make some glioblastoma cells in the tumor resistant to chemo- and radiation therapy.
“Glioblastomas are among the most treatment-resistant of cancers, so new strategies are greatly needed,” Guo says.
Published in the journal Cancer Discovery.