Targeted therapy for cancer stem cells: the patched pathway and ABC transporters.
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.
Lou
H
H
National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Dean
M
M
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects*
D018528:ATP-Binding Cassette Transporters