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!
GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University
Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
25.04.2018 | Physics and Astronomy
25.04.2018 | Physics and Astronomy
25.04.2018 | Information Technology