| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2035675 | Cell | 2012 | 14 Pages |
SummarySelective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use of differentiation as a therapeutic strategy.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (3372 K)
Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (329 K)Download as PowerPoint slideHighlights► Neoplastic hPSCs provide a robust generalizable screening model for human CSCs ► Compounds that induce hPSC differentiation selectively target somatic CSCs ► Thioridazine selectively targets leukemic stem cells while sparing normal HSCs ► Dopamine receptor pathway provides a candidate biomarker of human CSCs
