Lung cancer: Molecular scissors determine therapy effectiveness

Mar 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 , 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 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 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. 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. "

More information: 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

Source: Helmholtz Association of German Research Centres

Explore further: AstraZeneca cancer drug, companion test approved

add to favorites email to friend print save as pdf

Related Stories

Cancer-resistant mouse discovered

Nov 27, 2007

A mouse resistant to cancer, even highly-aggressive types, has been created by researchers at the University of Kentucky. The breakthrough stems from a discovery by UK College of Medicine professor of radiation medicine Vivek ...

A genetic 'gang of 4' drives spread of breast cancer

Apr 11, 2007

Studies of human tumor cells implanted in mice have shown that the abnormal activation of four genes drives the spread of breast cancer to the lungs. The new studies by Howard Hughes Medical Institute researchers reveal that ...

Recommended for you

Putting the brakes on cancer

Dec 19, 2014

A study led by the University of Dundee, in collaboration with researchers at our University, has uncovered an important role played by a tumour suppressor gene, helping scientists to better understand how ...

Peanut component linked to cancer spread

Dec 19, 2014

Scientists at the University of Liverpool have found that a component of peanuts could encourage the spread and survival of cancer cells in the body.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.