Among these is an antibody called cetuximab, which attaches to a protein molecule that is found in large amounts on the surface of many types of cancer cells. When this surface molecule, called epidermal growth factor receptor, or EGF-R for short, is blocked by cetuximab, the cancer cell receives less signals stimulating cell division.
Clinical studies of non-small cell lung cancer, which is the most frequent type of lung cancer, have shown so far that only part of the patients treated with cetuximab benefit from the treatment. Therefore, doctors are urgently searching for biomarkers which reliably predict responsiveness to the antibody therapy.
Professor Heike Allgayer heads the Department of Experimental Surgery of the Mannheim Medical Faculty of the University of Heidelberg and the Clinical Cooperation Unit "Molecular Oncology of Solid Tumors" at DKFZ. The scientist suspects that the therapeutic antibody can disarm, in particular, individual cancer cells that have detached from the primary tumor, invade other tissues and grow into secondary tumors there. Therefore, Allgayer and her team focused on lung cancer cells' ability to metastasize. Indeed, the investigators were the first to show in lung cancer cell lines that cetuximab inhibits growth and invasion of cancer cells and reduces the frequency of metastasis.
For invading surrounding healthy tissue, cancer cells needs specific proteins which act like molecular scissors to cut a trail for them. One of these cutting tools is the u-PAR protein which is considered a marker molecule for the invasion ability of cancer cells. Allgayer's team found out that cancer cells produce less u-PAR after treatment with cetuximab: The antibody appears to block the cell's u-PAR production.
Allgayer's team also showed that non-small cell lung cancer is resistant to cetuximab treatment, in particular, when the cancer cells produce large amounts of u-PAR. When the researchers switched off u-PAR production using a genetic trick, the cells responded to cetuximab again.
"Our results show, for the first time, that u-PAR might be an indicator of the effectiveness of cetuximab treatment in non-small cell lung cancer," Heike Allgayer says. "The more u-PAR the cells produce, the less they are responsive to the drug." This conclusion is in line with first observations made in lung cancer patients. Tumor cells of patients who did not respond to cetuximab usually produced higher amounts of the molecular scissors u-PAR.
It came as a surprise for Allgayer that EGF-R itself, the target molecule of the drug cetuximab, did not correlate with responsiveness. Further investigations are needed to verify these results. "We want to find possibilities to prescribe the drug only for those patients who can actually benefit from it," says Allgayer, a doctor and scientist. "Finding suitable biomarkers is one of the most urgent tasks when introducing novel, target-specific therapeutics."
Nikolova DA, Asangani IA, Nelson LD, Hughes DPM, Siwak DR, Mills GB, Harms A, Buchholz E, Pilz LR, Manegold C, Allgayer H: Cetuximab attenuates metastasis and u-PAR expression in non-small cell lung cancer: u-PAR and E-cadherin are novel biomarkers of Cetuximab sensitivity. Cancer Research 2009, DOI: 10.1158/0008-5472.CAN-08-3236
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is the largest biomedical research institute in Germany and is a member of the Helmholtz Association of National Research Centers. More than 2,000 staff members, including 850 scientists, are investigating the mechanisms of cancer and are working to identify cancer risk factors. They provide the foundations for developing novel approaches in the prevention, diagnosis, and treatment of cancer. In addition, 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 funded by the German Federal Ministry of Education and Research (90%) and the State of Baden-Württemberg (10%).
Dr. Sibylle Kohlstaedt | EurekAlert!
Further reports about: > Antibody > Biomarker > Cancer > Cetuximab > DKFZ > Deutsches Krebsforschungszentrum > EGF-R > Molecular Target > Molecular scissors > antibody therapy > cancer cells > cell division > lung cancer > metastasis > protein molecule > risk factor > specific key molecules tumor cells > tumor cells > u-PAR protein
New type of photosynthesis discovered
17.06.2018 | Imperial College London
New ID pictures of conducting polymers discover a surprise ABBA fan
17.06.2018 | University of Warwick
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...
Water molecules exist in two different forms with almost identical physical properties. For the first time, researchers have succeeded in separating the two forms to show that they can exhibit different chemical reactivities. These results were reported by researchers from the University of Basel and their colleagues in Hamburg in the scientific journal Nature Communications.
From a chemical perspective, water is a molecule in which a single oxygen atom is linked to two hydrogen atoms. It is less well known that water exists in two...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
15.06.2018 | Materials Sciences
15.06.2018 | Ecology, The Environment and Conservation
15.06.2018 | Power and Electrical Engineering