One of the most troublesome, and potentially fatal, complications of malignant mesothelioma is the accumulation of liquid in the pleural cavity — so-called malignant pleural effusion. A study showed that the drug cysmethynil was able to reduce the volume of liquid in the pleura of a mouse model of mesothelioma, suggesting it could represent a new approach to treating the disease manifestation.
When tumor cells infiltrate the pleura — the membrane lining the lungs — they disrupt the permeability of blood vessels, causing liquid to accumulate in the pleural cavity. The resulting pleural effusion is associated with poor prognosis and short survival.
Current treatments are merely palliative, most often employing different drainage techniques, and are often associated with side effects and discomfort. Few patients are actually known to benefit from the treatment, and an urgent need exists for more efficient treatment options.
Cysmethynil belongs to a class of compounds that blocks the activation of small GTPases, factors that promote several cancer features such as cell expansion and migration. GTPases are also involved in changing the blood vessel permeability and promoting ingrowth of vessels into tumors. Since these processes are involved in the development of pleural effusions, the research team from the National and Kapodistrian University of Athens, Greece, figured that the drug might be effective in reducing pleural effusions associated with malignant mesothelioma.
The study, “Icmt inhibition exerts anti-angiogenic and anti-hyperpermeability activities impeding malignant pleural effusion,” revealed that cysmethynil effectively reduced effusions by reducing blood vessel permeability. It also slowed recruitment of new blood vessels into the tumor.
The findings, published in the journal Oncotarget, showed that mice treated with cysmethynil had higher numbers of macrophages, cells known to fight tumors. When the researchers studied cancer cells together with macrophages in cell cultures, they observed that the macrophage cells took on a more tumor-promoting appearance. The research team stopped this development by adding cysmethynil to the cell culture.
While other studies have investigated the role of this drug class to inhibit tumor growth, this study is the first to show that a drug in this group could prevent malignant pleural effusion. Cysmethynil should, therefore, be explored as a potential therapy targeting this severe complication of malignant mesothelioma.