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Starving cancer cells of cholesterol might offer a new way to treat brain tumors
Date:9/15/2011

ival of 15 months after diagnosis. The tumors are difficult to surgically remove because malignant cells invade surrounding brain tissue.

In addition, genetic differences leave some glioblastoma cells in the tumor resistant to chemo- and radiation therapy, the researchers say.

"Some glioblastomas respond well to treatment initially when the therapy-sensitive cells are killed, but the tumor then returns relatively quickly as the therapy-resistant cells proliferate," says co-author Dr. Arnab Chakravarti, chair and professor of Radiation Oncology and co-director of the OSUCCC James Brain Tumor Program.

"Because glioblastomas are among the most treatment-resistant of cancers, new therapeutic strategies are urgently needed," says Chakravarti.

The study used tumor-cell lines, cells from patients and an animal model. Key technical findings include the following:

  • In nearly 50 percent of glioblastomas, a mutation called EGFRvIII hyperactivates the PI3K signaling pathway and a master transcriptional regulator called SREBP-1.

  • Activating this pathway upregulates the low-density lipoprotein (LDL) receptor and promotes LDL uptake, enabling tumor cells to import large amounts of cholesterol that feed tumor-cell growth and survival.

  • Pharmacological activation of the nuclear Liver X Receptor leads to the loss of LDL receptors and to upregulation of the ABCA1 protein pump, which transports cholesterol out of the malignant cells. Together, these actions starve tumor cells of cholesterol, causing their death.

"Because this pathway is activated in other types of cancer, this work may have significant implications for a broad range of cancer types," Mischel says.


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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

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