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Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells

Eleftherios Sachlos1, Ruth M Risueño, Sarah Laronde

  • 1McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.

Cell
|May 29, 2012
PubMed

Insights

Thioridazine, an antipsychotic, selectively targets cancer stem cells (CSCs) by antagonizing dopamine receptors. This discovery supports using differentiation as a therapeutic strategy and highlights dopamine receptors as potential cancer biomarkers.

Area of Science:

  • Oncology
  • Stem Cell Biology
  • Pharmacology

Background:

  • Selective targeting of cancer stem cells (CSCs) is crucial for novel therapeutics.
  • Existing assays for human CSCs and normal stem cells are limited for biological screening.

Purpose of the Study:

  • To identify small molecules that selectively target and induce differentiation in neoplastic cells.
  • To explore the potential of targeting dopamine receptors on CSCs.

Main Methods:

  • Utilized a discovery platform comparing neoplastic and normal human pluripotent stem cells (hPSCs).
  • Screened libraries of known compounds to identify molecules inducing differentiation.
  • Investigated the effect of thioridazine on CSCs and normal stem cells in vitro and in vivo.

Main Results:

  • Thioridazine selectively targets neoplastic cells and impairs human somatic CSCs.
  • Normal blood stem cells were unaffected by thioridazine.
  • Dopamine receptors, expressed on CSCs and breast cancer cells, are antagonized by thioridazine.

Conclusions:

  • Neoplastic hPSCs are valuable for identifying CSC-targeting drugs.
  • Differentiation is a viable therapeutic strategy for overcoming neoplastic self-renewal.
  • Dopamine receptors may serve as biomarkers for various malignancies.

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