Stem cells in breast tumours: are they ready for the clinic?

The concept of stem-like cells in cancer has been gaining currency over the last decade or so since evidence for stem cell activity in human leukaemia and solid tumours, including breast cancer, was first published. The evidence established that sub-populations of cells identified by antibodies to cell surface markers behaved like developmental stem cells in their capacity to re-grow the human tumour for several generations in experimental immune-deficient hosts. The experiments established that cells with tumourigenic capacity expressed 'cancer stem cell' (CSC) markers and that activity could also be measured by self-renewal of tumour sphere colonies in culture. In breast and other cancers, there is good evidence that CSCs are relatively resistant to radio- and chemotherapy indicating that novel CSC-targeted therapies are needed. Several pathways are promising targets in breast CSCs. There are several ways of combating CSC activity including inducing their apoptosis, inhibiting stem cell self-renewal to either stop their division or to promote their differentiation, or targeting the CSC niche that supports them. The first challenge for developing novel CSC therapies is to ascertain which of these CSC properties is being targeted. The second challenge is to determine suitable CSC biomarkers to measure the efficacy of the novel CSC therapies. We propose using biomarkers as a means to identify and assess CSC activity in clinical trials. This is likely to be demanding but feasible in the near future. Thus, we asked if CSCs are ready for the clinic, however, the emerging question becomes: is the clinic ready for cancer stem cells?