Moreover, it is often impossible to identify all the fine extensions by which the tumor spreads into surrounding healthy tissue. To at least slow down the growth of tumor cells that have remained in the head, almost all glioblastoma patients are treated by radiotherapy after surgery.
"Unfortunately, we can only delay cancerous growth in this way, but we cannot cure patients. The tumor cells, especially the cancer stem cells, are very resistant to radiation," says Prof. Dr. Dr. Peter Huber, who is head of the Clinical Cooperation Unit 'Radiation Oncology' at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ).
Studies conducted in recent years found that response to radiation therapy in various cancers is better when certain types of cellular growth factors are blocked at the same time. Glioblastoma cells often produce large amounts of a growth factor called TGF-β (transforming growth factor beta). High levels of TGF-β in these tumors are correlated with particularly aggressive growth and a poor prognosis. In addition, the factor seems to support the self-renewal capability of glioblastoma stem cells. "We therefore suspect that blocking TGF-β signaling pathways slows down the self-renewal of cancer stem cells and, thus, may improve radiation treatment outcomes," Peter Huber adds, explaining the background of the study now published.
In collaboration with colleagues from, among others, the Radiology Department of Heidelberg University Hospitals and a DKFZ department led by Prof. Dr. Ana Villalba, Huber's team investigated the effect of a combination of radiation treatment and a newly developed substance called LY2109761. This substance blocks the signals that are transmitted into cells by the TGF-β receptor. The investigators first studied glioblastoma cells in tissue samples taken during surgical removal of the tumors. Irradiation combined with adding the substance reduced the self-renewal capability of tumor stem cells and delayed their growth significantly better than radiation treatment alone.
The group transplanted human glioblastoma cells into the brains of mice and found that these animals, after receiving the combination therapy, survived longer than those animals treated by radiotherapy alone. Tissue studies showed that, under the combination therapy, tumors grew more slowly and less invasively and showed a lower density of newly formed blood vessels. "Paradoxically, radiation therapy can provoke aggressive growth behavior in surviving tumor cells. LY2109761 seems to prevent this fatal effect," says Huber, explaining how the drug seems to work.
Blocking of TGF-β signaling produced such promising results that researchers will now conduct a multicenter clinical trial to find out whether this mechanism may also slow down glioblastoma growth in patients more effectively than the current standard treatment. Led by Prof. Dr. Wolfgang Wick, who is head of a collaboration unit of DKFZ and the Neurology Department of Heidelberg University Hospitals, the combination therapy will be tested in Germany (Heidelberg), Spain, and the U.S.A.
Mengxian Zhang, Susanne Kleber, Manuel Röhrich, Carmen Timke, Na Han, Jochen Tuettenberg, Ana Martin-Villalba, Jürgen Debus, Peter Peschke, Ute Wirkner, Michael Lahn and Peter E. Huber: Blockade of TGF-beta signaling by the TGFβR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Cancer Research 2011, DOI:10.1158/0008-5472.CAN-11-1212
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 2,500 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg where promising approaches from cancer research are translated into the clinic. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. The center is a member of the Helmholtz Association of National Research Centers. Ninety percent of its funding comes from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.
Dr. Sibylle Kohlstädt | EurekAlert!
The genes are not to blame
20.07.2018 | Technische Universität München
Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences