By discovering how a deadly form of brain cancer is supplied with cholesterol, researchers have uncovered a potential new strategy to treat glioblastoma.
Their study, published online today in the journal Cancer Discovery, is part of a growing cancer research effort aimed at starving cancer cells of blood and other life-sustaining components rather than killing them outright.
“Our data demonstrate that glioblastoma cells need large amounts of cholesterol to grow and to survive,” said lead investigator Paul Mischel, MD, of the David Geffen School of Medicine at the University of California, Los Angeles.
“This is not surprising, considering the critical role of cholesterol in making new membranes, of which rapidly growing tumors need a lot,” he added.
Mischel and his colleagues studied glioblastoma cells in animals and in tissue taken from patients with cancer. They found that a mutation in the gene that encodes epidermal growth factor revs up a signaling pathway known as PI3K, which triggers increased production of low-density lipoprotein that feeds cancer cells. They were able to activate a transcription factor that pumped cholesterol out of the cancer cells and caused their death.
“Our findings suggest that the development of drugs to target this pathway may lead to significantly more effective treatments for patients with this lethal form of brain cancer,” Mischel noted.
Glioblastoma is among the most deadly of all cancers. Median survival from the time of diagnosis is 12 to 15 months, even with aggressive therapy. Some patients with glioblastoma respond well to initial treatment, but quickly become resistant to therapy.
“Because this pathway is activated in other types of cancer, this work may have significant implications for a broad range of cancer types,” Mischel said.