Fig. 1

The Role of the CSC Hierarchy in Tumourigenesis. a Cancer Stem Cell (CSC) Theory indicates that tumourigenesis begins with rapid proliferation of stem cell-like tumour-initiating cells known as CSCs (Orange). Once a pool of CSCs has been established, less-potent ‘Progenitor CSCs’ are produced via differentiation, which our data indicate can be sensitive (white) or (green) resistant to conventional cancer therapies. These Progenitor CSCs differentiate to produce the mature cells (Brown) that constitute the bulk of the primary tumour. As the tumour becomes established, active CSCs (Orange) can enter a dormant state known as Quiescence (Red). b We propose an alternative model for hierarchical CSC structure where both CSCs and Progenitors can be sensitive or resistant to standard cancer therapies. Clinical-targeting of all CSC and Progenitor types is likely to compromise tumourigesis, which is an attractive clinical strategy. However, to efficiently treat refractory disease, this model suggests that it may be important to identify, model and target the specific therapy-resistant component(s) of the CSC hierarchy