Researchers continue to focus on biomarkers as a target to increase the effectiveness of existing treatments for malignant mesothelioma. These genetic characteristics can be used to indicate the progress of mesothelioma, help determine an appropriate treatment, and assess the effectiveness of that treatment. Now, researchers have identified a biomarker that they believe points to poor prognosis in mesothelioma patients, but that could also lead to a promising therapeutic approach for the asbestos-caused cancer.
Researchers from Japan report the urokinase-type plasminogen activator receptor (uPAR), also known as CD87, that is normally expressed throughout the body, including in the colon and kidneys, was found at elevated levels in a mouse model with mesothelioma. The team from Nagoya University Graduate School of Medicine, Nagoya, Japan, found that the higher the level of uPAR, the worse the prognosis was for the mice.
“For the first time, we showed that uPAR overexpression is observed in asbestos-induced rat MM [malignant mesothelioma], regardless of the asbestos fibers used for carcinogenesis and the histological subtype of MM,” wrote the authors. “These data indicate that uPAR overexpression is a common and important expressional alteration in MM.”
The researchers then went on to discover that overexpression of uPAR is also associated with sensitivity to the platinum-based chemotherapy drug cisplatin. When they blocked the level of uPAR in the mice, there was a rise in the sensitivity to cisplatin. On the contrary, higher levels of uPAR “significantly decreased cisplatin sensitivity.”
According to the National Institute of Environmental Health Sciences, marker levels may be measured before treatment to help doctors plan the appropriate therapy. In some types of cancer, the level of a tumor marker reflects the stage (extent) of the disease and/or the patient’s prognosis (likely outcome or course of disease).
Mesothelioma is an aggressive, terminal cancer found in the lining of the lungs, heart and abdomen in patients previously exposed to asbestos. Although the cancer has been shown to be chemo-resistant, chemotherapy continues to be one of the primary treatment protocols for the disease, with the preferred combination being gemcitabine and cisplatin.
Patients nearly always develop resistance to chemotherapy, leading to metastasis of the cancer. However, studies like this where research is done to identify ways to increase the sensitivity, and thus the effectiveness, of cisplatin, and potentially other existing treatments, can lead to an increase in patient survival.
“In addition to the potential use of uPAR as a prognostic marker, the combination of uPAR abrogation and cisplatin may reveal a promising therapeutic approach for MM,” the researchers concluded.”
See the Sept. 2 issue of Oncotarget for the full report.