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Identification of selective inhibitors of cancer stem cells by high-throughput screening.

Cell | 2009

Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs.

Pubmed ID: 19682730 RIS Download

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Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R03 MH089663

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ChemBank (tool)

RRID:SCR_007592

ChemBank is a public, web-based informatics environment that includes freely available data derived from small molecules and small-molecule screens, and resources for studying the data so that biological and medical insights can be gained. ChemBank is intended to guide chemists synthesizing novel compounds or libraries, to assist biologists searching for small molecules that perturb specific biological pathways, and to catalyze the process by which drug hunters discover new and effective medicines. ChemBank stores an increasingly varied set of cell measurements derived from, among other biological objects, cell lines treated with small molecules. Analysis tools are available and are being developed that allow the relationships between cell states, cell measurements and small molecules to be determined. Currently, ChemBank stores information on hundreds of thousands of small molecules and hundreds of biomedically relevant assays that have been performed at the ICG in collaborations involving biomedical researchers worldwide. These scientists have agreed to perform their experiments in an open data-sharing environment. The goals of ChemBank are to provide life scientists unfettered access to biomedically relevant data and tools heretofore available almost exclusively in the private sector. We intend for ChemBank to be a planning and discovery tool for chemists, biologists, and drug hunters anywhere, with the only necessities being a computer, access to the Internet, and a desire to extract knowledge from public experiments whose greatest value is likely to reside in their collective sum.

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