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Researchers Turn To Experimental Drug to Improve The Effectiveness of Chemotherapy Against Mesothelioma

Red Blood Vessels

Researchers are turning to an experimental, metal-based anti-cancer drug to increase the effectiveness of chemotherapy in mesothelioma patients. While chemotherapy is used in the treatment of nearly all pleural mesothelioma patients, the cancer eventually develops a resistance to the drugs rendering them ineffective. However, by first treating the patient with the ruthenium-containing drug RAPTA-T, the mesothelioma tumors may more readily absorb the chemotherapy and slow the growth.

A team of researchers from the Centre Hospitalier Universitaire Vaudois, Switzerland, and the Swiss Federal Institute of Technology, determined that in order to be effective, chemotherapy drugs must first reach the tumor with the help of blood vessels, then break through the tumor tissue to deliver the toxic liquid to the cancer cell. But, the researchers discovered that abnormal blood vessels in mesothelioma cancer cells can build up a pressure in the cell tissue that keeps out the chemotherapy drugs.

Researchers often focus on developing  therapies that halt the growth of blood vessels since new blood vessels fuel mesothelioma tumor growth. The Swiss researchers, however, believed that by doing the opposite and normalizing and aiding the growth of blood vessels in mesothelioma tumors the chemotherapy could be better absorbed.

The team turned to the experimental compound RAPTA-T, still undergoing pre-clinical evaluation, known to enhance tumor vasularization, to test their theory.  In mouse models of human pleural mesothelioma cancer cells, when RAPTA-T was administered prior to cisplatin there was reduced tissue pressure and increased oxygenation in the tumor. This opened the door to the chemotherapy, and the researchers report this led to higher levels of cisplatin in the tumor and “enhanced mesothelioma growth inhibition.”

“By combining RAPTA-T with cisplatin, one of the first-line chemotherapeutic agents for mesothelioma, we demonstrate improved treatment outcome through higher chemotherapeutic drug uptake into the tumor,” noted the authors in a July 6 article in Scientific Reports.

Pleural mesothelioma is a rare form of cancer caused by exposure to airborne asbestos fibers. The cancer, that affects just 3,000 Americans each year, is highly aggressive and is resistant to many current mesothelioma treatments. Use of platinum-based chemotherapy, including cisplatin, is considered effective against mesothelioma, but the relief is often short-lived with the cancer eventually recurring. Enhancing the effectiveness of this approved treatment with a novel therapy could bring extended survival to mesothelioma patients.

The metal platinum is shown to stop cells from multiplying, but the platinum-based drugs have significant side effects. Ruthenium, the newest metal compound being used to fight cancer, is less toxic than platinum causing fewer side effects, and also halts tumor growth and metastasis.

“These results suggest a chemotherapeutic combination therapy with RAPTA-T as a novel option in resectable and advanced  mesothelioma,” the team concluded.

Significantly more research still needs to be conducted with RAPTA-T, but these initial findings bring hope that researchers are uncovering new ways to target the terminal cancer.

Read the full study in the July 6 issue of Scientific Reports.

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Last Modified: March 4, 2019

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