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Lung cancer: Molecular scissors determine therapy effectiveness
Date:3/17/2009

In the past few years, a number of anti-cancer drugs have been developed which are directed selectively against specific key molecules of tumor cells. 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
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Contact: Dr. Sibylle Kohlstaedt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

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