Limitations of the cancer stem cell theory

Cancer stem cells (CSCs) can be operationally defined as a subset of neoplastic cells which are responsible for the growth and re-growth of primary and metastatic tumors. Although the existence of perpetually dividing cells is a logical necessity to explain the malignant properties of human tumors, experimental data supporting their existence have only recently been obtained. New knowledge in basic stem cell biology and the availability of several cell surface markers for the definition and isolation of small subsets of immature cells coupled to the use of the classical model of xenotransplantation in immune deficient mice has identified putative CSCs in several solid tumors such as mammary, colon, brain, pancreas, prostate, melanoma and others. However, the theory must be considered as still in its infancy, since tumors grown in mice only partially recapitulate the biology of human cells. In addition, whether the "transformed" cell is the neoplastic counterpart of a normal stem cell or whether complete malignant behaviour can occur in a more differentiated cell has still to be demonstrated. In spite of these difficulties, the CSC hypothesis could be of clinical relevance, especially in the definition of new ways to assay drug sensitivity of primary human tumors.