Doctors at Kobe University in Hyogo, Japan say the enzyme, called orotate phosphoribosyltransferase (OPRT), plays an important role in the inhibition of RNA synthesis which, in turn, can influence the development and spread of malignant mesothelioma.
A New Target for Mesothelioma Therapy?
To test whether this enzyme could potentially be a target for a new kind of mesothelioma treatment, the team enrolled 15 malignant pleural mesothelioma patients who were diagnosed between July 2004 and December 2013.
They measured the levels of several different enzymes in these patients, among them OPRT and thymidylate synthase (TS), the primary enzyme targeted by the mesothelioma chemotherapy drug pemetrexed (Alimta).
“We found that OPRT expression was extremely high in malignant pleural mesothelioma tissue,” writes lead study author Yoichiro Hamamoto of the National Hospital Organization Disaster Medical Center in Tokyo. In fact, more than 85 percent of mesothelioma patients tested had very high OPRT expression.
Implications for Mesothelioma Treatment
Pemetrexed is the number one first-line chemotherapy drug for mesothelioma, but it is only effective part of the time. There is no consensus on the best second-line option.
The Japanese researchers decided to treat their study participants, who had failed first-line treatment, with a drug called S-1. Like pemetrexed, S-1 inhibits TS, but it also inhibits RNA synthesis through the OPRT pathway.
“We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory malignant pleural mesothelioma,” reports Dr. Hamamoto. “This case also showed high OPRT protein expression.”
The team concludes that S-1 has potential as a new treatment for mesothelioma, not only because it inhibits TS, but also because of its interaction with OPRT.
Pleural mesothelioma is a highly aggressive and treatment-resistant malignancy of the lung lining caused by asbestos exposure. This is the first study to focus on OPRT expression in mesothelioma patients.
Hamamoto, Y, et al, Orotate phosphoribosyltransferase is overexpressed in malignant pleuralmesothelioma: Dramatically responds one case in high OPRT expression, April 5, 2016, Rare Diseases, eCollection 2016