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Targeted therapy for cancer stem cells: the patched pathway and ABC transporters

Abstract

Data from certain leukemias as well as brain and breast cancer indicate that there is a small population of tumor cells with ‘stem cell’ characteristics and the capacity for self-renewal. The self-renewing cells have many of the properties of normal stem cells and have been termed ‘cancer stem cells’. These cancer stem cells make up as few as 1% of the cells in a tumor, making them difficult to detect and study. Like normal stem cells, cancer stem cells have a number of properties permitting them to survive traditional cancer chemotherapy and radiation therapy. These cells express high levels of ATP-binding cassette (ABC) drug transporters, providing for a level of resistance; are relatively quiescent; have higher levels of DNA repair and a lowered ability to enter apoptosis. Combined cancer therapy approaches targeting the cancer stem cells and the non-stem cells may be developed with increased efficacy. Efforts to target the Hedgehog/Patched pathway, critical to embryonic growth and differentiation, and the ABCG2 drug efflux transporter will be presented.

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Acknowledgements

Dedicated to George Vande Woude for teaching me (MD) to think big and take chances. This study was supported with Federal funds from the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Correspondence to M Dean.

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Lou, H., Dean, M. Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 26, 1357–1360 (2007). https://doi.org/10.1038/sj.onc.1210200

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  • DOI: https://doi.org/10.1038/sj.onc.1210200

Keywords

  • cancer stem cell
  • hedgehog/patched pathway
  • smoothened
  • ABC transporters
  • ABCG2
  • cyclopamine

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