Development of Glioblastoma Slowed when Targeted with Cholesterol-lowering Drugs

Glioblastoma with extreme nuclear enlargement.
Glioblastoma with extreme nuclear enlargement.

Glioblastoma is the mostcommon,most aggressive and untreatableform of malignant primary brain tumors in humans involving the glial cells. The disease accounts for 52% of allfunctional tissue brain tumor cases and 20% of all intracranial tumors andoccurs in only 2?3 cases per 100,000 people in Europe and North America. Median survival times are between12 to 15 months. Because glioblastoma is resistant to conventional therapies, including the most aggressive chemotherapy and radiotherapy, the desease is dificultto treat. Othercomplicating factors include the fact thatthe brain is susceptible to damage due to conventional therapy and has onlya very limited capacity to repair itself. Furthermore,only a few drugs can cross theblood-brain barrier to act on the tumor.

However,scientists have now 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. ?New treatments are needed, 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.?


Last Page Update: September 15, 2011

Featured Image:Very high magnification micrograph showing extremely profound nuclear enlargement in a glioblastoma. HPS stain. The nuclear enlargement (meganucleus) and atypia seen in these images is hard to surpass. It is very uncommon. Glioblastoma is one of the deadliest tumours known. The median survival is measured in months and only about 5% can expect to survive more than three years. Courtesy: ? 2011 Nephron. Used with permission.

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