Mesothelioma researchers there are evaluating an immune system modulator called FTY720 or fingolimod. Derived from a fungus called Iscaria sinclairii, FTY720 has been used to treat the relapsing form of multiple sclerosis.
Although FTY720 has shown what the research team calls “therapeutic potential” in some other forms of cancer, this is the first study evaluating the agent in the treatment of malignant pleural mesothelioma.
FTY720 and Mesothelioma Treatment
To test the impact of FTY720 on mesothelioma tumors, the researchers first treated a panel of mesothelioma cell lines as well as normal human mesothelial cells. They assessed the action of the agent by measuring the activity of phosphatase protein 2A (PP2A), a major target for FTY720.
The next step was to evaluate the activation of programmed cell death or apoptosis. A breakdown in apoptosis signaling is a major reason why cancers like malignant mesothelioma are allowed to grow out of control.
Finally, the team gave the FTY720 treatment to mice that had been infected with human mesothelioma tumors to look for negative side effects.
A New Mesothelioma Therapy?
The University of Hawaii researchers found that FTY720 “significantly suppressed” the viability of mesothelioma cells without affecting normal mesothelial membrane cells.
The drug inhibited the activity of PP2A by displacing a protein that is overexpressed by mesothelioma cells but not by normal cells. The result was an increase in programmed cell death in the laboratory-grown mesothelioma cells.
“Moreover, FTY720 administration in vivo [in a live subject] effectively reduced tumor burden in mice without apparent toxicity,” writes study author Agata Szymiczek, a molecular biology research specialist, in the Journal of Translational Medicine.
This is significant because toxicity is a major reason why most mesothelioma patients do not see lasting results from standard chemotherapy; if patients received enough of these agents to permanently destroy their tumors, the side effects would be lethal.
Next Steps for FTY720
Although FTY720 has already been shown to be helpful in people with some types of multiple sclerosis, it is not an approved drug for treating malignant mesothelioma.
This preclinical study is the first step toward formal testing of the drug for that purpose.
Malignant pleural mesothelioma is an extremely rare cancer caused by exposure to asbestos. Conventional cancer treatments are only moderately effective and most patients have a life expectancy of a year or less.
Qualified mesothelioma patients may choose to participate in a clinical trial in order to gain access to new and experimental mesothelioma treatment options.
Szymiczek, A, et al, “FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model”, March 2017, Journal of Translational Medicine