Clapper, Patti, Schweizer and Mason

A joint international study between the Cancer Biology Proteomics Group at the Postgraduate Medical Institute of the University of Hull, Hull York Medical School in Hull, UK and the Queens Centre for Oncology and Haematology in Hull and East Yorkshire examined an alternate method of treating malignant pleural mesothelioma – the most aggressive and untreatable form of the asbestos cancer. 

The researchers specifically targeted Malignant Pleural Mesothelioma (MPM) because even after decades of studying how this disease affects individual patients, the median survival rate remains tragically low.  Pleural mesothelioma is a type of cancer caused by asbestos fibers that enter the body and imbed themselves in the pleura, the soft tissue that surrounds internal organs such as the lungs.   

In an effort to help develop more effective treatments, researchers took a look at epidermal growth factor receptors (EGFR) in various mesothelioma cases.  They found that the growth factor is often over-expressed in samples taken from MPM patients at rates between 44% and 97%, and would therefore make an excellent subject for targeted anti-mesothelioma compounds.

Such targeted treatments have been used, with varying success, to treat other, less virulent forms of cancer including non-small cell lung cancer.  Typically, doctors would use tyrosine kinase inhibitors and, in some cancer patients, introduce anti-EGFR antibodies.  Thus far, however, such treatments have shown little promise in mesothelioma patients.  Still, the leads of this new study felt the method had merit enough to continue with their research. 

Rates of MPM diagnoses in the U.K. have continued to rise while in the United States MPM rates peaked a while ago and are now dropping, though other forms of mesothelioma are still on the rise.  U.K. health officials, however, suggest that their rates won’t peak for another 4 years.  In any case, MPM remains a tremendous threat.  And regardless of citizenship, a malignant pleural mesothelioma patient can only expect to live, on average, for nine months after the disease is discovered. 

As with other less-aggressive forms of cancer, the traditional treatment for mesothelioma has included chemotherapy, surgery, and radiation treatments.  However, the current method of research suggests that biologically attacking the tumors themselves in a targeted fashion rather than blanket approaches will see better results.  Thus this new look at EGF inhibitors.

Epidermal growth factor (EGF) was discovered in 1960 by Stanley Cohen during his work with mice.  He later confirmed that he same mechanism was at work in humans in 1975.  Essentially, the growth factor is a protein which tells cells when to grow and when not to grow.  In mesothelioma patients, the growth factor is damaged or overactive and this defect aids in the growth of cancerous tumors.

By specifically attacking EGF, researchers hope to be able to at least slow tumor growth, if not reverse it.  However, only two types of compounds have been found to effectively interfere with the way EGF works:  anti-EGFR monoclonal antibodies (mAb's) and small molecule tyrosine kinase inhibitors (TKI's).

As yet, neither has shown to have significant effects on MPM tumors in humans, however, certain compounds have been shown to radically alter the growth patterns of MPM cells in laboratory situations.  Specifically, Gefitinib, which inhibits growth of MPM cells through reducing the effectiveness of “transduction pathways”, and PD153035, which reduces cell motility in MPM samples are two compounds being researched.

Scientists had hoped that by creating a combined treatment using a multimodal method to attack MPM with EGF inhibitors as part of the solution they can find a mix that does work.

To that end, the study concluded that more research into the effectiveness of EGF in humans is warranted.