Navigation Links
Why don't brain tumors respond to medication?
Date:9/1/2009

Malignant brain tumors often fail to respond to promising new medication. Researchers in Heidelberg have discovered a mechanism and a tumor marker for the development of this resistance. A "death receptor" can possibly provide information as to how great the chances of success are for chemotherapy. At the same time, it offers a new approach for promising brain tumor therapy.

Dr. Wolf Mller, senior consultant in the Neuropathology Department at the Institute of Pathology of Heidelberg University Hospital, and his team were able to show that certain brain tumors (astrocytomas) can deactivate a crucial protein on their cell surface, the so-called death receptor. The medication docks onto this receptor and causes the cells to die. An intact "death receptor" can thus serve as a tumor marker for whether or not a therapy has a chance of success. The study was conducted with funding from the Tumor Center of Heidelberg/Mannheim and was published in the journal Clinical Cancer Research.

Primary brain tumors that develop from brain cells, in particular their most malignant variant the glioblastoma, have a very poor prognosis. Although various kinds of therapies are attempted, patients with a glioblastoma usually die within two years of diagnosis. The researchers are thus working at high speed to become more familiar with the biology of these tumors in order to develop more efficient treatment.

"Death receptor" can be switched on and off

The researchers in Heidelberg examined various primary brain tumors (astrocytomas, which also include glioblastomas) and discovered that the gene for the death receptor DR4 was switched off in up to 75 percent of cases by what is known as "promoter methylation". This means that methyl groups accumulate at the segment of the gene that is crucial for its activity (expression). The gene's information can thus no longer be read, the gene is silenced.

The death receptor DR4 is an attractive target for receptor-specific therapy. Fortunately, an already-existing drug, Mapatumumab, an antibody protein, binds directly to the receptor and can trigger the death of the cell. This drug is currently being tested in a number of clinical studies (Phase II) for other solid tumors, e.g. lung cancer.

New approach for a specific therapy for brain tumor cells

For gliomas, treatment with Mapatumumab appears to be particularly interesting as the death receptor is usually found only on tumor cells, not on other brain cells. Since glioma growth is especially invasive into brain tissue, surgical removal is impossible and chemotherapy is very difficult. Chemotherapy with Mapatumumab could reach all tumor cells and kill them while sparing healthy brain cells without receptors.

In cell culture trials, the researchers have already been successful in reversing methylation and making the "death receptors" functional again tumor cells reacted to the drugs and died off. If gene expression was again suppressed, the cells became resistant again.

"Therapies that are capable to switch on specific individual genes by these manipulations do not yet exist. But being aware of the tumor markers can point the way for the development of new therapies whose goal is gene manipulation," explained Dr. Wolf Mller. Targeted examinations of tumor tissue prior to therapy can now make it possible to identify patients with an intact death receptor. These patients have good conditions for benefiting from the promising therapy, while other patients would at least be spared the side effects of useless treatment.


'/>"/>

Contact: Dr. Wolf C. Mller
Wolf.Mueller@med.uni-heidelberg.de
062-215-639-912
University Hospital Heidelberg
Source:Eurekalert

Related biology news :

1. Periodontitis and myocardial infarction: A shared genetic predisposition
2. Invasion of the brain tumors
3. HIV is a double hit to the brain
4. AIDS interferes with stem cells in the brain
5. 60 second test could help early diagnosis of common brain diseases
6. U of MN researchers discover noninvasive diagnostic tool for brain diseases
7. U of Minnesota researchers discover noninvasive diagnostic tool for brain diseases
8. Influence of sex and handedness on brain is similar in capuchin monkeys and humans
9. Inside the brain of a crayfish
10. Specific brain protein required for nerve cell connections to form and function
11. Brains timing linked with timescales of the natural visual world
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/9/2016)... NEW YORK , March 9, 2016 ... current and future states of the RNA Sequencing (RNA ... in segments such as instruments, tools and reagents, data ... Analyze various segments of the RNA-Sequencing market such ... RNA-Sequencing services Identify the main factors affecting each segment ...
(Date:3/9/2016)... , March 9, 2016  Crossmatch ® , ... enrollment solutions, today announced the addition of smart ... Altus multi-factor authentication platform. New contextual and ... to step-up security where it,s needed most — ... Washington, DC . --> ...
(Date:3/3/2016)... 2016  FlexTech, a SEMI Strategic Association Partner, awarded ... & Development, Leadership in Education, and, in a category ... th year of the FLEXI Awards and the ... from past years . Judging was done on ... of criteria, by a panel of non-affiliated, independent, industry ...
Breaking Biology News(10 mins):
(Date:4/29/2016)... Denver, CO (PRWEB) , ... April 29, 2016 ... ... on addressing the necessary fundamentals to transform technology into a viable company, CereScan’s ... enable growth. Mr. Kelley, a recognized leader and mentor in the Denver ...
(Date:4/29/2016)... , April 29, 2016 ... the latest update to its industry-leading treatment planning software, ... that Monaco version 5.11 provides ... now attain calculation speeds up to four times faster ... . With the industry,s gold standard Monte ...
(Date:4/28/2016)... ... April 28, 2016 , ... Connecticut Innovations ... companies, today announced the launch of VentureClash , a $5 million global ... , “VentureClash looks to attract the best early-stage companies here in Connecticut, around ...
(Date:4/28/2016)... ... April 28, 2016 , ... ... an open house for regional manufacturers at its Maple Grove, Minnesota technical center, ... Hardinge Group, Chiron and Trumpf. Almost 20 leading suppliers of tooling, accessories, ...
Breaking Biology Technology: