Possible new pathway can overcome glioblastoma resistance

January 24, 2012, American Association for Cancer Research

Glioblastoma, a lethal brain cancer, is one of the most resistant to available therapies and patients typically live approximately 15 months.

Previous research has focused on the activation of the apoptosis, or cell death, pathway using therapeutic agents such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); however, the vast majority of these experiments have been stymied by resistance.

"Scientists in this field have been hoping to treat this cancer with this new type of apoptosis pathway-targeted therapeutic drug, and this new information may provide a path forward," said Chunhai "Charlie" Hao, M.D., Ph.D., a neuropathologist at Emory University.

Using human glioblastoma samples and tumor-initiating cells or cancer , Hao and colleagues identified a possible new pathway for targeted therapies. Results of their work are published in Cancer Discovery, the newest journal of the American Association for Cancer Research.

TRAIL treatment often leads to caspase-8-mediated apoptosis. However, study results showed that the A20 E3 ligase is highly expressed in and together with receptor interacting protein 1 (RIP1) and caspase-8, forms a signaling complex. Upon TRAIL interaction with this complex, the A20 E3 ligase triggers ubiquitination of RIP1, interferes with activation of caspase-8 and prevents caspase-8-initiated apoptosis.

"Previous research in this area has been unable to overcome the obstacle created by resistance. This research shows one of the mechanisms for how we can manipulate the ubiquitination process to overcome the resistance to the apoptosis-targeted cancer therapies," said Hao.

Understanding the mechanisms of resistance is vital to developing therapies going forward, according to Hao.

Explore further: Molecule Nutlin-3a activates a signal inducing cell death and senescence in primary brain tumors

Related Stories

Molecule Nutlin-3a activates a signal inducing cell death and senescence in primary brain tumors

April 20, 2011
Researchers of Apoptosis and Cancer Group of the Bellvitge Biomedical Research Institute (IDIBELL) have found that a small molecule, Nutlin-3a, an antagonist of MDM2 protein, stimulates the signalling pathway of another protein, ...

Researchers to publish paper in Molecular Cancer journal

December 7, 2011
(Medical Xpress) -- Erxi Wu, assistant professor of pharmaceutical sciences, and Fengfei Wang, research associate in pharmaceutical sciences, co-wrote the article, "β2-adrenoceptor blockage induces G1/S phase arrest ...

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.