Newswise — A group of researchers including 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). Study authors also include Federica Gemignani, Ph.D, Chair of Genetics at University of Pisa, Irene Dell’anno, Ph.D., University of Pisa, and Sarah A. Martin, PhD, Senior Lecturer at Barts Cancer Institute, London, UK.
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 Sbarro Health Research Organization (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.