Fig. 1

Different models of tumor heterogeneity. a Clonal evolution or stochastic model suggests that serial acquisition of mutations generates tumor cell heterogeneity and all cells are capable of renewal and tumorigenesis. b According to the cancer stem cell (CSC) model, tumors are organized into a hierarchy of heterogeneous cell populations, and only a small subset of cells within a tumor called CSCs have the ability to sustain tumor formation. CSCs have the ability to perpetuate themselves through self-renewal and generate large populations of more differentiated descendants by unidirectional conversion. c Phenotype plasticity model posits that irreversibly differentiated cells can be converted back to an undifferentiated state or stem cell-like state given the appropriate stimulus. This dynamic bidirectional conversion between CSC and non-CSC can give rise to tumor heterogeneity