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Renal cancer drug may inhibit growth of mesothelioma cells, enhance chemo effects

Researchers in Austria report that temsirolimus, a drug used to treat kidney cancer, may slow the growth of malignant pleural mesothelioma cells.


Temsirolimus is an inhibitor of mammalian target of rapamycin, mTOR, a protein that regulates cell growth. It was approved by the U.S. Food and Drug Administration in May, 2007 as an intravenous drug for the treatment of renal cell carcinoma.


In laboratory tests using both cell cultures and animal models, the researchers found that temsirolimus blocked the mTOR gene pathway responsible for signaling the growth and division of mesothelioma cells. That had a cytostatic, or growth-stopping, effect on the malignant cells.


The tests also showed that mesothelioma cells that were resistant to cisplatin, a widely used chemotherapy drug, showed hypersensitivity against temsirolimus, leading the researchers to suggest that combining the drug with chemotherapy could be an effective treatment.


The study, “Temsirolimus inhibits malignant pleural mesothelioma growth in vitro and in vivo: synergism with chemotherapy,” was published in the May issue of the Journal of Thoracic Oncology.


The lead investigator, Walter Berger, of the Institute of Cancer Research at the Medical University of Vienna, said the study could lead to clinical trials involving mTOR inhibitors as a novel treatment strategy for mesothelioma, a deadly disease of the lung and abdominal lining caused by asbestos exposure.


 "In our preclinical study… we were able to demonstrate that inhibition of the major oncogene mTOR is active against human mesothelioma especially after development of chemotherapy resistance both in vitro and in vivo," Berger said.


Mesothelioma is often resistant to chemotherapy, with response rates that range from 15 to 50 percent, depending on the drug. Many researchers are focusing on combination treatments that enhance the effects of chemotherapy to improve survival times for mesothelioma patients. Fewer than ten percent of patients diagnosed with the disease survive more than 10 years, and most die within 18 months.