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Targeting cholesterol may help slow glioblastoma

PHILADELPHIA Glioblastoma is among the most lethal cancers, but scientists have uncovered a novel growth mechanism that suggests patients with glioblastoma could be treated with cholesterol-lowering agents, according to a study published in Cancer Discovery, the newest journal of the American Association for Cancer Research.

Lead researcher Paul Mischel, M.D., Lya and Harrison Latta professor of pathology and laboratory medicine, and professor of molecular and medical pharmacology at the David Geffen School of Medicine at the University of California, Los Angeles, said the study revealed that EGFR vIII, a known oncogene in glioblastoma, increased the activity of the LDL receptor and, therefore, allowed for large amounts of cholesterol.

"Our data demonstrate that glioblastoma cells need large amounts of cholesterol to grow and to survive. This is not surprising considering the critical role of cholesterol in making new membranes, of which rapidly growing tumors need a lot," said Mischel.

Mischel's work is part of a growing body of cancer research where scientists study how they can combat a tumor's growth supply, rather than the tumor itself. The most familiar agents in this arena are the vascular endothelial growth factor inhibitors, like bevacizumab, which restrict a tumor's blood supply.

If this laboratory work is confirmed in larger studies, it could lead to a role for cholesterol-manipulating drugs in the treatment of glioblastoma, he said.

"Pharmacologic strategies that pump cholesterol out of a cell could lead to significant tumor cell death," said Mischel.

Glioblastoma is currently one of the most lethal cancers. With median survival times of 12 to 15 months, it is often resistant to even the most aggressive chemotherapy and radiotherapy.

"New treatments are needed," he said. "This study uncovers a novel and potentially therapeutically targetable tumor cell growth and survival pathway, which could potentially lead to more effective treatments for patients in the clinic."


Contact: Jeremy Moore
American Association for Cancer Research

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