A small non-coding RNA molecule, miR-34a, could become the centerpiece of a therapy to treat diffuse malignant peritoneal mesothelioma (DMPM), a rare subtype of malignant mesothelioma, a study indicates.
The miR-34a molecule inhibits the cancer’s ability to grow and migrate, triggering tumor-cell death. Finding a way to activate this pathway could lead to a treatment, Italian researchers said. A non-coding RNA molecule is one that is not translated into a protein.
The study, “Antitumor activity of miR-34a in peritoneal mesothelioma relies on c-MET and AXL inhibition: persistent activation of ERK and AKT signaling as a possible cytoprotective mechanism,” was published in the Journal of Hematology & Oncology.
DMPM accounts for only 30 percent of mesothelioma cases, but it’s very aggressive, and there are few treatment options. Little is known about why it is so virulent and resistant to chemotherapy.
Researchers examined DMPM tissue samples from 45 patients who had cytoreductive surgery and chemotherapy. Doctors delivered the concentrated, heated hyperthermic intraperitoneal chemotherapy (HIPEC) directly to patients’ abdomens during surgery.
The patients’ tissue samples were compared with seven peritoneum tissue samples from healthy patients, and five cell lines developed in a laboratory. The peritoneum is a membrane lining the abdominal cavity and covering abdominal organs.
DMPM samples were grouped in three categories. One was epitheliod, the most common type of mesothelioma, which has good treatment responses. The second was sarcomatoid, which is less common and is the most resistant to therapy. The third was biphasic, whose characteristics fall between the other two.
Researchers found lower levels of miR-34a in the DMPM tissue samples and cell lines than in the samples taken from healthy subjects. But they failed to find a correlation between the microRNA levels and the patients’ clinical stage.
That suggested that miR-34a could suppress DMPM tumors but couldn’t be used as a biomarker to distinguish the different stages of disease.
Experiments in animal models and laboratory cultures showed that a substance mimicking miR-34a inhibited DMPM cell growth and migration, triggering cell death.
Researchers also found that miR-34a’s tumor-suppressor activity relied on the inhibition of the proteins c-MET and AXL, which are known to support tumor growth and progression. That suggested that further studies of miR-34a, c-MET, and AKL could be a path to a treatment.
“Our preclinical data showing impressive inhibitory effects induced by miR-34a on DMPM cell proliferation, invasion, and growth in immunodeficient mice strongly suggest the potential clinical utility of a miR-34a-replacement therapy for the treatment of such a still incurable disease,” the researchers wrote.
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