Targeting Cholesterol May Help Slow Glioblastoma

• These lethal brain cancers depend on cholesterol for growth.

• Laboratory findings identified a tumor survival pathway.

• Glioblastoma is one of the most untreatable cancers.

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.”

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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. The AACR publishes seven major peer-reviewed journals: Cancer Discovery; Cancer Research; Clinical Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Prevention Research. AACR journals received 20 percent of the total number of citations given to oncology journals in 2010.

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