Repositioning approved drugs for the treatment of problematic cancers using a screening approach.
Advances in treatment strategies together with an earlier diagnosis have considerably increased the average survival of cancer patients over the last four decades. Nevertheless, despite the growing number of new antineoplastic agents introduced each year, there is still no adequate therapy for problematic malignancies such as pancreatic, lung and stomach cancers. Consequently, it is important to ensure that existing drugs used to treat other types of cancers, and potentially other diseases, are not overlooked when searching for new chemotherapy regimens for these problematic cancer types. We describe a screening approach that identifies chemotherapeutics for the treatment of lung and pancreatic cancers, based on drugs already approved for other applications. Initially, the 1280 chemically and pharmacologically diverse compounds from the Prestwick Chemical Library® (PCL) were screened against A549 (lung cancer) and PANC-1 (pancreatic carcinoma) cells using the PrestoBlue fluorescent-based cell viability assay. More than 100 compounds from the PCL were identified as hits in one or both cell lines (80 of them, being drugs used to treat diseases other than cancer). Selected PCL hits were further evaluated in a dose-response manner. Promising candidates for repositioning emanating from this study include antiparasitics, cardiac glycosides, as well as the anticancer drugs vorinostat and topotecan.
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.|Biomolecular Screening Facility, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Hristo P
http://orcid.org/0000-0003-4450-7332
HP
Varbanov
Biomolecular Screening Facility, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Fabien
F
Kuttler
Biomolecular Screening Facility, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Damiano
D
Banfi
Biomolecular Screening Facility, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Gerardo
G
Turcatti
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Paul J
PJ
Dyson
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058492:Drug Repositioning; D004354:Drug Screening Assays, Antitumor; D057166:High-Throughput Screening Assays; D006801:Humans
D000970:Antineoplastic Agents