Featured Research

from universities, journals, and other organizations

Why Don't Brain Tumors Respond To Medication?

Date:
September 2, 2009
Source:
University Hospital Heidelberg
Summary:
Malignant brain tumors often fail to respond to promising new medication. Researchers in Germany 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.

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.

Related Articles


Dr. Wolf Müller, 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 Müller. 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.



Story Source:

The above story is based on materials provided by University Hospital Heidelberg. Note: Materials may be edited for content and length.


Journal Reference:

  1. Agnes Elias, Markus D Siegelin, Albert Steinmüller, Andreas von Deimling, Ulrike Lass, Bernhard Korn, Wolf Mueller. Epigenetic Silencing of Death Receptor 4 Mediates Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Resistance in Gliomas. Clinical Cancer Research, 2009; 15 (17): 5457 DOI: 10.1158/1078-0432.CCR-09-1125

Cite This Page:

University Hospital Heidelberg. "Why Don't Brain Tumors Respond To Medication?." ScienceDaily. ScienceDaily, 2 September 2009. <www.sciencedaily.com/releases/2009/09/090901104850.htm>.
University Hospital Heidelberg. (2009, September 2). Why Don't Brain Tumors Respond To Medication?. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2009/09/090901104850.htm
University Hospital Heidelberg. "Why Don't Brain Tumors Respond To Medication?." ScienceDaily. www.sciencedaily.com/releases/2009/09/090901104850.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) — The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) — Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins