Drug Screening Finds Existing Agents with Potential Activity Against Thyroid Cancer
Researchers have increasingly begun to evaluate existing approved drugs for other clinical uses in an effort to circumvent the extensive process of drug discovery and development. A study accepted for publication in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM) has found that a number of drugs that are already approved for use in a broad range of therapeutic categories express an antiproliferative effect in thyroid cancer cell lines.
Using quantitative high-throughput screening of the National Institutes of Health Chemical Genomic Center's pharmaceutical collection (a compilation of 2,816 clinically approved drugs and bioactive compounds), researchers at the National Human Genome Research Institute, Bethesda, MD, found that agents with the greatest anti-cancer effectiveness within thyroid cancer cell lines included cardiotonic and antiobesity agents. Sixteen drugs had an efficacy of greater than 60% and 50% inhibitory concentration in the nanomolar range.
Results of the quantitative high-throughput screening were validated using the agents bortezomib and ouabain in cell lines with BRAF V600E, RET/PTC1, p53, and PTEN mutations, as well as different histological subtypes of thyroid cancer. Both bortezomib and ouabain induced apoptosis, and ouabain caused cell cycle arrest.
The study investigators believe that such a screening approach can lead to the discovery of novel agents in different therapeutic categories and drugs which are not currently classified as chemotherapy agents by their mechanisms of action. Furthermore, following the approach of the study may lead to drug repurposing and accelerated clinical trials of compounds with well-established pharmacokinetics and toxicity profiles.
Zhang L, He M, Zhang Y, et al. Quantitative High-Throughput Drug Screening Identifies Novel Classes of Drugs with Anticancer Activity in Thyroid Cancer Cells: Opportunities for Repurposing. J Clin Endocrinol Metab. 2011 Dec 14. [Epub ahead of print]