The multiple sclerosis therapy Fingolimod (FTY720) reduced tumor size in a mouse model of malignant mesothelioma (MM), a study demonstrated.
The research, “FTY720 Inhibits Mesothelioma Growth In Vitro And In A Syngeneic Mouse Model,” was published in the Journal of Translational Medicine.
MM, an aggressive cancer with poor patient prognosis, can often develop resistance to most therapeutic approaches. Patients live a median of 12 to 13 months after diagnosis. Current standard of care treatment, a combination of Platinol (cisplatin) and Alimta (pemetrexed) chemotherapy, extends their lives by only 11 weeks.
This means there is a need for novel approaches to targeting mesothelioma cells.
FTY720 is an immunosuppressant that has been approved for treating multiple sclerosis (MS). Recent studies have suggested that it also suppresses tumors in a variety of cancers. No research had been done on whether it could treat MM, however.
“The development of new therapeutic agents for rare cancers, such as MM, is hampered by the increasing costs of research and drug development from the laboratory to the patient’s bed,” a research team from the University of Hawaii Cancer Center wrote. “Drug repurposing, which involves finding new uses for existing drugs that are outside the scope of their original indication, is a strategy that drastically reduces time and costs to bring a new drug to the market.”
Agata Szymiczek, the first author of the study, and her colleagues are with the center’s Thoracic Oncology Program.
The team looked at FTY720’s impact on cultures of MM cells and human mesothelial cells (HM). The drug reduced MM growth and significantly increased MM cell death without affecting normal HM cells, they discovered.
Biochemical analysis showed that FTY720 works by affecting a protein called SET that is usually found in high levels in MM cells. SET is a natural regulator of phosphatase protein 2A (PP2A), a tumor suppressor that is often impaired in MM. FTY720 reactivated the protein, allowing it to exert its anti-tumor effects, the researchers learned.
The drug also promoted the activation of several molecular mechanisms that lead to cell death, they discovered.
FTY720 reduced tumor size in mice with MM with no apparent adverse side effects, they added.
“Our data represent a proof of principle for the efficacy of FTY720 in MM therapy, with no apparent toxicity in our mouse model,” Szymiczek and her colleagues wrote. “FTY720 and its second-generation derivatives potentially fit the criteria for drug repurposing and can be promising anticancer agents for the treatment of MM, most likely in combination with existing or novel therapies.”
