Anti-Alcoholism Drug from 1950s Shows Promise in Treating Mesothelioma
An FDA-approved drug used since the 1950s to treat alcoholism has shown considerable promise in suppressing the spread of mesothelioma and enhancing the effectiveness of chemotherapy, according to a recently published study.
Scientists and clinicians conducted the study, published April 2014 in PLOS ONE, to examine the effects of copper-enhanced disulfiram (DSF-Cu) on malignant pleural mesothelioma cells in vitro and on animal models.
Arun K. Rishi, Ph.D., of the Karmanos Cancer Institute at Wayne State University, said the findings could clear a path to more effective treatment options for the cancer caused almost exclusively by exposure to asbestos fibers.
“A drug like this could have the potential to localize the disease and prevent its spread,” Rishi told Asbestos.com. “That’s very exciting.”
Long-time mesothelioma specialist Harvey Pass, M.D., director of thoracic surgery at New York University Medical Center, also co-authored the study.
Effective against Other Cancers
Previous studies had shown the effectiveness of disulfiram against breast, lung and colon cancer cells, leading to the anticipation of positive results with mesothelioma. The next step before possible approval by the U.S. Food and Drug Administration (FDA) for the treatment of mesothelioma would be a Phase I clinical trial.
Disulfiram, which is sold under the brand name Antabuse, works in the treatment of alcoholism on a molecular level by changing the way alcohol is metabolized in the body.
Consuming alcohol while taking Antabuse typically results in uncomfortable symptoms: nausea, headaches, dizziness and vomiting. It is designed to end any cravings for alcohol. There are currently an estimated 200,000 patients in the United States taking the drug. Doctors also have used it to break cocaine abusers of the habit.
Researchers recently found that in certain cancer cell types, disulfiram mixed with copper will trigger apoptosis, a natural process that causes cells to commit suicide. The drug can eliminate damaged cells without causing local inflammation or long-term toxicity, which has made it an intriguing possibility in certain cancer therapies.
Mice with Mesothelioma Tumors
Researchers used the drug in laboratory cell cultures and on mice injected with human mesothelioma cells. Mice were treated with varying doses of disulfiram to help determine the most effective amount.
Researchers found that injecting DSF-Cu into mice stopped the growth of mesothelioma tumors and made them more susceptible to certain chemotherapy drugs.
A multimodal approach that includes surgery, chemotherapy and radiation is the most effective treatment for mesothelioma, which is diagnosed in roughly 3,000 people annually in the United States. Using only chemotherapy has not been enough to stop the disease consistently.
Mesothelioma, which has a long latency period (10-50 years) between exposure to asbestos and definitive symptoms, usually starts in the thin lining around the lungs.
“As a scientist, you’re looking for new avenues. A new mechanism to block the spread of this disease,” Rishi said. “To find something in the lab that could work is very significant.”
Doctors have used disulfiram for more than 60 years in the management of alcoholism. The FDA gave official approval in 1951 for that use. Clinical trials are currently testing the drug on various cancers.
- Rishi, Arun, Ph.D., professor, Department of Oncology and Internal Medicine, Karmanos Cancer Institute, Wayne State University, interview with Asbestos.com.
- Cheriyan, V. et al. (2014, April 1). Disulfiram Suppresses Growth of the Malignant Pleural Mesothelioma Cells in Part by Inducing Apoptosis. PLOS ONE. Retrieved from http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0093711
- Soghoian, S. (2013, Dec. 9). Disulfiram Toxicity. Medscape. Retrieved from: http://emedicine.medscape.com/article/814525-overview