Key result
High-throughput screening of 1,280 approved drugs identified over 100 compounds, including antiparasitics and cardiac glycosides, that exhibited significant cytotoxicity against chemoresistant lung and pancreatic cancer cells.
A screening approach identified over 100 approved compounds, including antiparasitics and cardiac glycosides, as potential candidates for repositioning in the treatment of lung and pancreatic cancers.
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May identify repurposing candidates for chemoresistant cancers; hypothesis-generating and requires further validation before clinical consideration.
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.
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Varbanov et al. (2017) studied Lung and pancreatic cancer (in vitro). Prestwick Chemical Library compounds vs. DMSO (negative control) was evaluated on Cell viability (HTS score and IC50). High-throughput screening of 1,280 approved drugs identified over 100 compounds, including antiparasitics and cardiac glycosides, that exhibited significant cytotoxicity against chemoresistant lung and pancreatic cancer cells.
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