Figure 2
After oncogenesis, induced by an initial event (solid arrow) with or without supporting events (hashed arrow), cells differentiate to form a heterogeneous tumour. Two models have been proposed to explain this (A and B). The process of clonal evolution (C) is likely to underlie the ongoing development of certain tumour characteristics such as drug resistance. (A) Stochastic model. Variations in phenotype and biology result from intrinsic and extrinsic factors including niche interactions (=) and intercellular signalling (▴). These signals may be available to any cell at a particular time, with the correct combination of factors able to initiate the CSC programme, and therefore self-renewal (curved arrows) in any member of the population. (B) Hierarchy model. A tumour shows a hierarchy analogous to the normal tissue hierarchy, with a restricted pool of cells showing self-renewal (curved arrows) and differentiation potential. Differentiated tumour cells form the bulk of the tumour mass but are unable to self-renew. (C) Clonal evolution. An ongoing process, beginning before the clinical presentation, wherein sequential genetic and epigenetic changes result in a polyclonal population with differing survival potential under the selective pressure of therapy. Clonal evolution may be seen within tumours following either the stochastic or hierarchy model.
