Screening-based approach to discover effective platinum-based chemotherapies for cancers with poor prognosis

• DOI: 10.1371/journal.pone.0211268
• Publication Date: 2019-01-29T19:02:18Z
• Authors: Hristo P. Varbanov; Fabien Kuttler; Damiano Banfi; Gerardo Turcatti; Paul J. Dyson
• Keywords: Carboplatin; Topotecan

Drug combinations are extensively used to treat cancer and often selected according complementary mechanisms. Here, we describe a cell-based high-throughput screening assay for identification of synergistic between broadly applied platinum-based chemotherapeutics drugs from library composed 1280 chemically pharmacologically diverse (mostly FDA approved) compounds. The was performed on chemoresistant cell lines derived lung (A549) pancreatic (PANC-1) carcinoma, where combination regimens currently though with limited success. identified during the were validated by synergy quantification using index method via high content fluorescent microscopy analysis. New promising discovered this approach include compounds not as anticancer drugs, such cisplatin or carboplatin hycanthone spironolactone in deferoxamine non-small cancer. Strong topotecan PANC-1 cells, compared A549 suggests that combination, treatment regimens, could be carcinoma well. Several diseases other than cancer, including pyrvinium pamoate, auranofin, terfenadine haloprogin, showed strong cytotoxicity their own interactions platinum drugs. This study demonstrates non-obvious drug would based mechanisms can screening.