Breast cancer stem cell markers – the rocky road to clinical applications

The cancer stem cell model, a concept initially proposed more than a century ago, has been revisited with increasing enthusiasm in the past decade. This model proposes that tumors, like normal tissues, are organized in a cellular hierarchy, in which 'cancer stem cells' are the only cells with unlimited proliferation potential and therefore capable of driving tumor growth and metastasis. The 'differentiated' cancer cells that account for the majority of the tumor population may have high proliferation potential, but it is not unlimited. It follows that eliminating these differentiated progenies while sparing the cancer stem cells will ultimately result in relapse. The other component of the stem cell model of carcinogenesis holds that stem and progenitor cells are the cells susceptible to transformation, owing to their long life and high proliferative capacity.A paradigm-shifting hypothesis, the cancer stem cell model could potentially be the foundation for new preventive and therapeutic strategies in cancer. However, concerns regarding the validity of this model have been expressed, mostly regarding its experimental validation. It has been brought to attention that xenografting cancer cells in immunosupressed animals, the gold standard for testing cancer stem cell properties in vivo, may select for cells adaptable to the animal host, therefore introducing an unavoidable bias. Experts in the field cautioned against oversimplified views that do not take into account the genetic variability and clonal evolution of cancer cells, including those of cancer stem cells.The efforts of numerous recent studies focused on testing the validity and universality of this model across tumor types of various tissues, and on exploring its clinical implications. In line with these directions, the recent study by Honeth and colleagues [1] aims to identify possible correlations between the representation of tumor-initiating cells and classic molecular and histoclinical parameters that cl