System Identifies Drugs That Selectively Target Cancer Stem Cells

Cancer researchers have used a sophisticated screening system to search for small molecular weight compounds able to kill cancer stem cells (CSCs) without harming normal human pluripotent stem cells (hPSCs).

CSCs, which are highly resistant to chemical and radiation treatments, are thought to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for sufferers of metastatic disease.

Investigators at McMaster University (Hamilton, ON, Canada) using a discovery platform capable of revealing differences between CSCs and normal hPSCs identified small molecules from libraries of known compounds that induced cellular differentiation to overcome uncontrolled cancerous growth.

They reported in the May 24, 2012, online edition of the journal Cell that surprisingly, thioridazine, an antipsychotic drug, selectively targeted CSCs. Thioridazine blocked the growth of human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood hPSCs.

The drug worked by antagonizing dopamine receptors that are expressed on CSCs and on breast cancer cells but not on hPSCs.

“The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells; by changing them into cells that are noncancerous,” said senior author Dr. Mick Bhatia, professor of biochemistry and biomedical Sciences at McMaster University. “Now we can test thousands of compounds, eventually defining a candidate drug that has little effect on normal stem cells but kills the cells that start the tumor.”

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