Drug May Improve Chemotherapy for Mesothelioma

A medication used to slow the growth of kidney cancer may help improve the effectiveness of chemotherapy for mesothelioma.

Temsirolimus is a kinase inhibitor, which works by blocking the action of the abnormal protein that signals replication in cancer cells. It is often used to treat advanced renal cell carcinoma (RCC), a cancer that begins in the kidney.

But a team of researchers in Vienna has found that the drug also appears to inhibit the growth of malignant pleural mesothelioma (MPM) cells, both in cell cultures and in animal models. The researchers used temsirolimus to ‘turn off’ the gene pathway known as mammalian target of rapamycin (mTOR) in mesothelioma cells. The mTOR pathway is responsible for signaling the growth and division of mesothelioma cells. It has been found in this and previous studies to be activated in all three types of malignant pleural mesothelioma.

While the temsirolimus effectively blocked the mTOR-mediated signals and triggered a cytostatic (growth-stopping) effect on all mesothelioma cells, certain cells were especially sensitive to its effects. Mesothelioma cells that were resistant to cisplatin, a chemotherapy agent commonly used to treat MPM, showed hypersensitivity against temsirolimus. The researchers theorized that treating such cells with both types of medicine – temsirolimus and cisplatin – might be more effective.

They write, “Accordingly, cisplatin and temsirolimus exerted synergistic inhibition of the mTOR downstream signals and enhanced growth inhibition and/or apoptosis (cell death) induction in mesothelioma cells.” The temsirolimus was “highly active” again MPM cells in mice, both by itself and in combination with cisplatin.

The findings are important because mesothelioma is often highly resistant to chemotherapy. Any drug that could improve the effectiveness of chemotherapy for mesothelioma has the potential to improve survival in a disease that typically has a poor prognosis. Fewer than ten percent of patients diagnosed with mesothelioma survive beyond ten years. Therapies that harness the power of patients’ own immune systems to combat mesothelioma cells are the focus of many current research studies.

Sources:

Hoda, MA et al, “Temsirolimus Inhibits Malignant Pleural Mesothelioma Growth In Vitro and In Vivo: Synergism with Chemotherapy”, February 23, 2011, Journal of Thoracic Oncology. Epub ahead of print. Varghese, S et al. “Activation of the phosphoinositide-3-kinase and mammalian target of rapamycin signaling pathways are associated with shortened survival in patients with malignant peritoneal mesothelioma”, September 13, 2010. Epub ahead of print.