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:12/8/2016)... ... 2016 , ... SunView Software aims to redefine IT self-service ... engaging and easy to use. Coming off the heels of a successful launch ... plans to roll out new AI-powered self-service enhancements to help organizations implement effective ...
(Date:12/8/2016)... ... 2016 , ... California Senate Bill (SB) 863, signed into law in 2012, ... and 2014, according to CompScope™ Medical Benchmarks for California, 17th Edition , a ... study, medical payments per claim in California decreased 4 percent in 2013 and then ...
(Date:12/8/2016)... ... 2016 , ... The Dianne Michael Insurance Agency, an Ohio-based ... is embarking on a charity drive with the aim of generating support for ... or neglected senior dogs in the Cincinnati region, and LuvFurMutts volunteers also work ...
(Date:12/8/2016)... ... 08, 2016 , ... Coffey Agencies, a locally owned and ... in the northern Alabama and Georgia regions, is embarking on a charity drive ... has built a network of support and education facilities to develop and provide ...
(Date:12/7/2016)... Kenosha, Wisconsin (PRWEB) , ... December 07, 2016 , ... ... the extraordinary new MedMaster™ MPCNGX . The MPCNGX is a multi-function, sealed, LED ... the right amount of light where and when it’s needed. , A ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... 2016 Research and Markets has announced the ... offering. ... The global chromatography market to grow at a CAGR ... 2016-2020, has been prepared based on an in-depth market analysis with inputs ... prospects over the coming years. The report also includes a discussion of ...
(Date:12/8/2016)... Conn. , Dec. 8, 2016  Boehringer Ingelheim ... 2017 Corporate Equality Index (CEI). This is the ninth ... has been designated as a Best Place to Work ... Foundation, the CEI is a national benchmarking report on ... lesbian, gay, bisexual and transgender (LGBT) employees. ...
(Date:12/8/2016)... 2016  Avelas Biosciences, Inc., a clinical stage ... from diagnosis through treatment, today presented clinical trial ... study in breast cancer patients utilizing investigational drug ... Symposium. Jonathan Unkart , M.D., resident physician ... Health, delivered the presentation titled "Intraoperative tumor detection ...
Breaking Medicine Technology: