Brain tumor discovery could lead to new treatment

July 08, 2011

EMBARGOED UNTIL 12P.M. EST, Friday, July 8, 2011, Cleveland: Cleveland Clinic researchers have identified a cellular pathway that cancer stem cells use to promote tumor growth in malignant glioma, an aggressive brain tumor. The research - published in the July 8 issue of Cell - also found that existing medications block this cancer-promoting pathway and delay glioma growth in animal models, suggesting a new treatment option for these often fatal brain tumors.

Malignant gliomas account for more than half of the 35,000-plus primary malignant brain tumors diagnosed each year in the United States. Unfortunately, the outlook for patients with malignant gliomas is poor. For patients with the most severe, aggressive form of malignant glioma (grade IV glioma or glioblastoma multiforme), median survival is 9 to 15 months with the best available therapies. These treatments include surgery followed by radiation therapy with the chemotherapy temozolomide followed by additional temozolomide treatment.

Although differences in tumors between people were known to exist, researchers have only recently begun to understand the importance of differences between cancer cells within the same patient. Groups of cells within a glioma which promote brain tumor formation in animal models - called cancer stem cells - have been identified. These cancer stem cells are often resistant to radiation and chemotherapy, making them an important target for developing new and effective disease treatments.

In a recently published manuscript, a team of Cleveland Clinic researchers - led by Jeremy Rich, M.D., Chairman, and Anita Hjelmeland, Ph.D., of the Department of Stem Cell Biology and Regenerative Medicine of the Lerner Research Institute of Cleveland Clinic - define a novel molecular pathway that cancer stem cells use to promote tumor growth. Cancer stem cells produce elevated nitric oxide, a molecule whose role in cancer is not well defined but which has been linked to therapeutic resistance, evasion of cell death, and enhanced proliferation. Nitric oxide is produced in cancer stem cells through increased levels of the enzyme nitric oxide synthase 2 (NOS2); decreasing the level or activity of this enzyme reduces cancer stem cell growth. When drugs inhibiting the NOS2 enzyme were given to mice with gliomas, the growth of the tumors was delayed. Using the National Institutes of Health supported database of glioma specimen data, they also found that increased levels of this enzyme are associated with decreased survival of glioma patients. Targeting this pathway could therefore provide benefits for glioma patients.

Current therapies for cancer have many side effects, because they rely on the increased sensitivity of the cancer cells to drugs which are toxic to normal cells. It is therefore important to consider the potential side effects of any new proposed cancer treatment. The current study did compare the levels of the enzyme NOS2 and the effects of its inhibitors in cancer stem cells and normal neural stem cells. Normal neural stem cells have some similar properties as cancer stem cells from gliomas but cannot form tumors. Only cancer stem cells were found to depend on the enzyme for their growth. Drugs inhibiting the NOS2 enzyme were evaluated in patients for the treatment of other diseases and had minimal toxicity. The authors suggest that these drugs may therefore be useful for enhancing the effects of current therapies without adding a lot of side effects. NOS2 inhibitors may thereby pose a potential therapeutic breakthrough for this lethal disease.
-end-
About Cleveland Clinic

Celebrating its 90th anniversary, Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. It was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. About 2,800 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. Cleveland Clinic Health System includes a main campus near downtown Cleveland, nine community hospitals and 15 Family Health Centers in Northeast Ohio, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and opening in 2013, Cleveland Clinic Abu Dhabi. In 2010, there were 4 million visits throughout the Cleveland Clinic health system and 155,000 hospital admissions. Patients came for treatment from every state and from more than 100 countries. Visit us at www.clevelandclinic.org. Follow us at www.twitter.com/ClevelandClinic.

Lerner Research Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.