Study of promising anti-cancer drug extended to mesothelioma
An oral drug being tested for the treatment of multiple myeloma shows signs of effectiveness against pleural mesothelioma, especially when used in combination with the popular chemotherapy agent cisplatin.
In a study published in the online open-access medical journal PloS ONE, Italian researchers report that the drug perifosine inhibits an enzyme that is part of the PI3K/AKT/mTOR pathway, a process that allows the proliferation of cancer cells.
The researchers tested the drug in the laboratory using human mesothelial cells and a variety of mesothelioma cell lines. They found that perifosine inhibits Akt1, a protein kinase that plays a role in multiple cellular processes that promote the growth of cancer cells. When used in combination with cisplatin, a standard chemotherapy for mesothelioma, the toxic effect on cancer cells was even greater.
“Data demonstrated that perifosine caused a dose-dependent reduction of Akt activation, at concentrations causing MMe cell growth arrest,” the researchers wrote. “This study provides a novel mechanism of action of perifisone, directly inhibiting EGFR/MET-Akt1/3 axis, providing a rationale for a novel translational approach to the treatment of MMe.”
Perifosine is being evaluated for a range of cancers, including in early-stage clinical studies in combination with chemotherapy and radiotherapy. Licensed by Æterna Zentaris Inc., perifosine has reached Phase III clinical trials for colorectal cancer and multiple myeloma. The Food and Drug Administration has granted perifosine “orphan drug” status for the treatment of multiple myeloma and neuroblastoma.
Earlier this year, researchers reported that a Phase III clinical trial of perifosine for treatment of colon cancer had failed to increase overall survival in the study group.
Mesothelioma is caused by asbestos exposure and is notoriously difficult to treat. Typically diagnosed in late stage, the disease kills most patients within 18 months. Even the most effective treatment — a combination of surgery, chemotherapy and radiation — has only shown modest improvements in patient survival.
Researchers have been exploring novel drugs, such as perifosine and bevacizumab, as well immunotherapies that boost the body's own disease-fighting capabilities, to improve outcomes.