Drug Repurposing Identifies New Candidates to Treat Mesothelioma

Antonio Giordano Luciano Mutti Marcella Barbarino

A group of researchers, led by Antonio Giordano, M.D., Ph.D., Director and Founder of the Sbarro Health Research Organization (SHRO), Temple University, in collaboration with Stefano Landi, Ph.D.,. Chair of Genetics at University of Pisa, Italy, have identified potential novel drug candidates for the treatment of Malignant Pleural Mesothelioma (MPM). 

MPM is a disease of the pleura related to asbestos exposure, which, despite the advancements in new therapeutic frontiers, has a dismal prognosis and very limited treatment options. 

The authors undertook a drug-repurposing approach that consists of evaluating existing drugs already approved for other human diseases. After screening 1170 drugs, they observed that cephalomannine, a taxane; ouabain, a cardiac glycoside; thonzonium bromide, an antifungal surfactant; and emetine, an emetic alkaloid, had marked activity against immortalized and patient-derived primary MPM cell lines. These compounds were shown to be promising, and they will be evaluated in further studies, both in vitro and in vivo. 

“We believe that drug repurposing is a valuable strategy to facilitate and accelerate the definition of novel treatment options for the management of MPM,” says Luciano Mutti, M.D., Adjunct Professor at Temple University and SHRO. 

The lack of effective therapies remains one of the main challenges, and drug repositioning could accelerate the identification of novel treatments. Biological assays were carried out for 41 drugs showing the highest cytotoxicity and for which there was a complete lack of published literature in MPM. 

The most active molecules were cephalomannine, ouabain, alexidine, thonzonium bromide, and emetine. Except for alexidine, these drugs inhibited the clonogenic ability and caspase activation in all cancer lines tested. The proliferation was inhibited also on an extended panel of cell lines, including primary MPM cells. The authors suggest that cephalomannine, ouabain, thonzonium bromide, and emetine could represent novel candidates to be repurposed for improving the arsenal of therapeutic weapons in the fight against MPM.

 

The paper was recently published in the journal Cancers.

 

About the Sbarro Health Research Organization

The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org