Cancer stem cells in breast cancer.

There is increasing evidence that cancer stem cells (CSCs) play a critical role in breast cancer initiation, progression, metastasis and drug resistance. It is thought that they are either generated from normal mammary stem/progenitor cells or from mammary epithelial cells by epithelial-mesenchymal transition. Breast CSCs are characterized by the activation of stemness-related pathways, such as the Notch and Wnt pathways, and by the expression of certain stem cell markers, such as CD44, EpCAM and ALDH1. CSCs form a minor population, whose proportion depends on various factors, including environmental conditions. Since CSCs are highly resistant to chemotherapy, additional treatment of breast cancer patients with CSC-specific drugs, such as salinomycin and gamma-secretase inhibitors which target the Wnt or Notch pathway, respectively, will be required. Interestingly, an equilibrium seems to exist between CSCs and non-stem cancer cells, and there are indications that CSCs can be recruited from non-stem cancer cells. As a consequence, it may be necessary to combine a therapy targeting CSCs with common chemotherapy that targets the bulk tumor to avoid the regeneration of CSCs.