Tumour stem cells and drug resistance

Stem-cell populations have been identified in a range of haematopoietic and solid tumours, and might represent the cell of origin of these tumours.Normal and cancer stem cells express high levels of ATP-binding cassette (ABC) transporters, such as ABCB1, which encodes P-glycoprotein, and the half-transporter ABCG2, which was originally identified in mitoxantrone-resistant cells.The drug-transporting property of stem cells conferred by ABC transporters is the basis for the 'side-population' phenotype that arises from the exclusion of the fluorescent dye Hoechst 33342.Cancer stem cells are likely to share many of the properties of normal stem cells that provide for a long lifespan, including relative quiescence, resistance to drugs and toxins through the expression of several ABC transporters, an active DNA-repair capacity and a resistance to apoptosis. Therefore, tumours might have a built-in population of drug-resistant pluripotent cells that can survive chemotherapy and repopulate the tumour.