Researchers in the Netherlands have unveiled what may be a major breakthrough in the chemotherapeutic treatment of malignant mesothelioma.
Malignant mesothelioma, a rare and virulent cancer caused by asbestos exposure, is notoriously resistant to standard cancer treatments, including chemotherapy.
Even the only chemotherapy drug specifically approved for the treatment of mesothelioma, Alimta (pemetrexed), only works for some patients. Now, a new study published in the Annals of Oncology suggests that a cellular transporter molecule called the proton-coupled folate transporter (PCFT) may help explain why.
Pemetrexed and Mesothelioma Treatment
Approved for the treatment of pleural mesothelioma and non-small cell lung cancer, pemetrexed is chemically similar to the B vitamin folic acid and is in the class of chemotherapy drugs called folate antimetabolites.
It works by inhibiting certain enzymes necessary for the growth and survival of mesothelioma cells.
To test the possible connection between PCFT and pemetrexed resistance, researchers at VU University Medical Center measured PCFT levels in both frozen tissue samples and immunohistochemical arrays in two groups of mesothelioma patients who had been treated with pemetrexed.
They found that the mesothelioma patients with the lowest PCFT levels tended to respond poorly to Alimta and, as a result, did not live as long as those whose levels were higher.
“Multivariate analysis confirmed PCFT’s independent prognostic role,” writes cancer researcher and lead author, Elisa Giovannetti. “Low PCFT protein levels were also associated with shorter overall survival.”
A First for Mesothelioma Research
The study represents the first time that PCFT has been identified as a potential prognostic biomarker for mesothelioma and the research team is calling for further study.
In the meantime, preclinical data suggest that a method they developed for promoting the formation of PCFT might be used to eradicate pemetrexed-resistant cells, allowing this gold standard mesothelioma treatment to work better for more patients.
An estimated 2,500 Americans are diagnosed with mesothelioma each year. Almost all of them will be recommended for chemotherapy with a combination of pemetrexed and cisplatin. A little less than a quarter of mesothelioma patients also undergo some type of surgery. Radiation is also frequently used either before or after surgery to reduce pain, shrink existing mesothelioma tumors, and prevent the seeding of new tumors.
Giovannetti, E, et al, “Role of proton-coupled folate transporter in pemetrexed-resistance of mesothelioma: clinical evidence and new pharmacological tools”, September 1, 2017, Annals of Oncology, Epub ahead of print