Researchers in Baltimore have made a significant discovery concerning the behavior of mesothelioma in varying patients. Their findings may help them to predict patient responses to the disease, and possibly even control those responses in order to improve survival in those with malignant peritoneal mesothelioma.

Peritoneal mesothelioma refers to the formation of cancerous tumors in the mesothelial tissues of the abdominal cavity. Like other forms of mesothelioma, the disease is caused almost exclusively by asbestos fibers and is terminal in the overwhelming majority of cases. Unlike better known forms of the disease such as pleural mesothelioma, or mesothelioma of the lung lining, the mechanism which introduces the asbestos fibers to the area of the tumor is unknown. Some evidence suggests that peritoneal mesothelioma may result from the accidental ingestion of asbestos fibers, whereas pleural mesothelioma results from inhalation of the dangerous materials.

Patients suffering from peritoneal mesothelioma react to the disease in very different ways, a fact which lead researchers to further investigation. According to the Maryland researchers, “There is marked variability in its clinical behavior. Some patients die rapidly, and others survive for many years.”

The researchers believe that the differences in individual responses to the disease may lie in the expression of certain genes which affect the chemical “signals” transmitted to cells. In some patients, these signaling pathways cause cancerous tumors to grow and spread more rapidly, while in other patients the tumors appear to grow far slower. The researchers analyzed forty-one tissue samples from mesothelioma patients, and found that the “signaling chemicals” responsible for RNA production and protein synthesis differed between samples.

In one group the over-expression of certain pathways known as PI3K and the mammalian target of mTOR caused the presence of specific genes associated with a peritoneal mesothelioma survival of around 24 months. In patients where the same pathways and the genes which they are linked to were not present, survival rates were more than twice that time at some 69.5 months. When synthetic means were introduced to inhibit the expression of the PI3K and mTOR pathways, they found that the division and growth of cancerous cells was significantly impeded.

The scientists believed that further research into the significance of specific gene expression in peritoneal malignant mesothelioma patients was warranted. They asserted that the experiments already conducted highlight the importance of analyzing gene expression and further understanding the mechanisms that link these expressions with differing survival rates.

The study concluded: “Targeting the PI3K and mTOR signaling pathways may have significant therapeutic value in patients with MPM.”

Southwest Oncology Group, one of the largest clinical trial cooperative groups in the United States, is conducting a new trial whose aim is to further understand a specific chemotherapy regimen used to fight malignant pleural mesothelioma.

Mesothelioma is a cancer of the mesothelium, a soft tissue found around the lungs, abdomen and heart which encases organ systems and promotes their smooth function. Pleural mesothelioma refers to the cancer when it attacks the lining of the lungs, or the pleural mesothelium.

Mesothelioma is a terminal disease, and is caused almost exclusively by exposure to asbestos fibers. When asbestos fibers are accidentally inhaled or ingested, they travel through the victim’s body until they become lodged in the mesothelial tissues. Asbestos fibers trapped in the mesothelium cause a scarring reaction which can spur the growth of malignant tumors.

Cancers in the body spread through cell division, and often require the development of new blood vessels to supply the malformed tumor tissues and continue growth. Chemotherapy aims to inhibit certain enzyme actions that are required for these cells to divide, thus slowing or stopping the growth of the tumor.

Mesothelioma is commonly treated with a specific chemotherapy treatment made up of both pemetrexed and cisplatin. While this treatment has demonstrated enough efficacy to become a commonly accepted mesothelioma treatment route, in many cases its effects are disappointing or even negligible. The Southwest Oncology Group is currently testing the effect of adding a third chemotherapy treatment to the regimen, cediranib maleate. The new treatment made up of all three chemotherapy drugs is being tested in patients who have not been treated previously for malignant mesothelioma with either surgery, chemotherapy, radiotherapy, hormonal therapy or any other form of treatment.

Cediranib maleate, which is also referred to as either AZD2171 or Recentin, is expected to stunt or stop the growth of new blood vessels which supply tumor growth with the nutrients necessary to grow and develop. This phase of the clinical trials, referred to as Phase I/II, is intended to study the side effects of the new treatment as well as discern the most effective dosage of the new additive.

Southwest Oncology Group is funded largely by the National Cancer Institute, and enrolls more than 6,000 cancer patients and healthy volunteers each year to study new drugs and treatment methods. Patients interested in participating in clinical trials of experimental drugs can contact the group for more details.