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

COLUMBUS, Ohio A new study suggests that blocking cancer cells' access to cholesterol may offer a new strategy for treating glioblastoma, the most common and deadly form of brain cancer, and perhaps other malignancies. The potential treatment could be appropriate for tumors with a hyperactive PI3K signaling pathway, which accounts for up to 90 percent of glioblastomas cases.

Researchers at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James) and at UCLA's Jonsson Comprehensive Cancer Center who led the study discovered that the hyperactive signaling pathway is linked to cholesterol metabolism, and that inhibiting this pathway leads to the death of glioblastoma cells in an animal model.

he findings are published in the journal Cancer Discovery.

"Our research shows that the tumor cells depend on large amounts of cholesterol for growth and survival, and that pharmacologically depriving tumor cells of cholesterol may offer a novel therapeutic strategy to treat glioblastoma," says first author and researcher Dr. Deliang Guo, assistant professor of radiation oncology at the OSUCCC James.

"This study uncovers a mechanism that links a common oncogene with altered cell metabolism, and it potentially offers a strategy for blocking that mechanism and causing specific tumor-cell death without significant toxicity," says principal investigator Dr. Paul S. Mischel, professor of pathology at UCLA's Jonsson Cancer Center and an adjunct professor of radiation oncology at the OSUCCC James.

"Overall, 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."

Glioblastomas strike about 18,500 Americans annually and kill nearly 13,000 of them. Glioblastoma multiforme is the most common and lethal form of the malignancy, with an average survival 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.


'/>"/>

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

Related medicine news :

1. Starving inflammatory immune cells slows damage caused by multiple sclerosis
2. Enhancing arrest of cell growth to treat cancer in mice
3. Paxil Blocks Tamoxifen, Lowers Survival Odds Against Breast Cancer
4. The National Coalition for Cancer Survivorship Joins the Commission on Cancer
5. Low forms of cyclin E reduce breast cancer drugs effectiveness
6. Racial disparities persist in the diagnosis of advanced breast cancer and colon cancer in the U.S.
7. Soft drinks may increase risk of pancreatic cancer
8. UH Case Medical Center researchers publish promising findings for advanced cervical cancer
9. Genes Play Role in Prognosis With Non-Small Cell Lung Cancers
10. Single gene mutation induces endometrial cancer
11. Certain genetic profiles associated with recurrence-free survival for non-small cell lung cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... ... process to promote standards of excellence for the field of eating disorders, announces ... 22 – 25, 2018 in Orlando, Florida at the Omni Resort at ChampionsGate. ...
(Date:10/13/2017)... ... ... Apple Rehab Shelton Lakes , which specializes in the delivery of ... part of a disaster drill on October 3rd. , Apple Rehab participated with the ... as well as the Connecticut Long Term Care Mutual Aid Plan (LTC-MAP). The ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Global Healthcare Management’s ... Alexandria Park in Milford, NJ. This free event, sponsored by Global Healthcare Management’s ... The fun run is geared towards children of all ages; it is a ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the ... danger possible to save lost souls in the Philippines. “The Journey: From the Mountains ... a dedicated teacher of the Bible. She has taught all ages and currently teaches ...
(Date:10/12/2017)... ... 12, 2017 , ... Planet Fitness, one of the largest and fastest growing ... open a flagship location in Covington, LA at 401 N. U.S. Highway 190, in ... to Office Depot in the Holiday Square shopping center. Its location allows it to ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... Divoti USA will engrave and process all non-coated ... latest FDA requirements, which stipulates new criteria regarding medical device manufacture ... Medical ID jewelry such as Medical ID Bracelets, can rest assured ... of the new FDA requirements . ... Divoti offers this dark mark fiber laser engraving process ...
(Date:10/11/2017)...  Caris Life Sciences ® , a leading innovator ... precision medicine, today announced that St. Jude Medical Center,s ... (POA) as its 17 th member. Through participation ... Cancer Institute will help develop standards of care and ... making cancer treatment more precise and effective. ...
(Date:10/10/2017)... COUNTY, Calif. , Oct. 10, 2017  NDS received FDA ... Mobile  — a medical-grade battery-powered display stand specifically designed for endoscopy ... to transform technology into a clinical solution to support the improvement ... Innovative Design ... ZeroWire Mobile Wireless Solution ...
Breaking Medicine Technology: