Figure 3.

Unified theory of tumor heterogeneity.

Notes: The dynamic nature of tumor initiation and progression is characterized by genetic and epigenetic insults on putative cancer cells and the microenvironment. The heterogeneity of the microenvironment includes varying densities of extracellular matrix, vasculature, immune cells, and oxygen concentration that places selective pressure on cancer cells. The genetic and epigenetic make-up of cells within tumors will vary from one region to the other. Some regions may be characterized by a BCSC hierarchy (A), stochastic plasticity (B), and clonal evolution (C) simultaneously, increasing its complexity.

Abbreviations: BCSC, breast cancer stem cells; ECM, extracellular matrix.