Mesothelioma Research Promises Improved Survival Rates

A team of researchers at the University Of Maryland School Of Medicine (in Baltimore, which houses the Marlene and Stewart Greenebaum Cancer Center) have isolated an auspicious way that may eventually improve survival rates for patients suffering from malignant peritoneal mesothelioma, or MPM.


Mesothelioma is cancer of the mesothelial linings that surround and protect the lungs, heart, and abdominal organs, the latter known as MPM.


According to researchers, in the U.S., 3,000 people per year are diagnosed with malignant mesothelioma. Of these, 15 to 20 percent have MPM, which exhibits as a large number of tumor nodules within the peritoneal cavity.


This form of mesothelioma is more common in females and young males, as opposed to pleural mesothelioma, which occurs most often in older males, and the diagnosis depends on a queue of symptoms that include severe abdominal swelling or distention, pain and weight loss.


Survival rates for MPM are currently less than two years, with surgery and chemotherapy forming a treatment standard limited to select patients. There is no cure for MPM, and while asbestos exposure is not mandatory for developing MPM, it is a highly causative factor, even though researchers agree that the disease is poorly understood.


The most difficult aspect of MPM is the fact that some patients die very quickly after diagnosis while others survive for several years, even without intervention. It was while attempting to discover why this discrepancy arises that university researchers, led by Sheelu Varghese, Ph.D., and H. Richard Alexander, M.D. of the university’s Division of Surgical Oncology, isolated the signaling pathways that trigger the growth and spread of cancer cells.


Working with tumor samples from 41 MPM patients, the researchers generated a global gene expression pattern and then compared them using a host of clinical parameters, (including patient survival rates, tumor histology, etc.) to determine the significance of each.


The tests resulted in the discovery of highly relevant discrepancies in the signaling chemicals responsible for protein manufacture and RNA production inside cells. One of these chemicals, phosphoinositide-3-kinase (PIK3CA, or PI3K) and a protein kinase that controls cell growth (and is poorly regulated in cancer), mTOR, were over-expressed, with the result that all the patients displaying this imbalance survived for an average of 2 years.

Where PI3K and mTOR were absent, the average survival rate was 5.5 years.

The obvious conclusion, according to researchers, was that evaluating the expression of these gene pathways and signaling mechanisms prior to treatment could help predict survival rates for MPM more accurately.

In addition, investigating the precise mechanism of these gene expression pathways may result in novel new gene therapies to cure MPM. This last was evaluated by the oral delivery of BEZ235, a dual-mechanism P13K and mTOR inhibition agent, which in trials “significantly” suppressed tumor growth in MPM tumors grafted into mice.

Researchers now hope to advance these experimental studies into patient clinical trials, which may result in an actual broad-spectrum cure, since age or sex is not a determining factor in MPM survival.

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