Figure 5.

Clonal Cancer Stemness. i) CSC Theory states that tumors are composed of multiple cell types produced by CSCs via multiple rounds of self-renewal and differentiation. ii) The Genetic Heterogeneity viewpoint states that cumulative acquired genetic mutations lead to genetically divergent cell lineages. CSC Theory and Genetic Heterogeneity are not mutually exclusive concepts. In fact, growing evidence suggests both are correct. iii) This points towards the Clonal Cancer Stemness model of malignancy, where both CSCs and genetic divergence account for the heterogeneous traits of malignancy (e.g. chemoresistance and metastasis). Additionally, CSC hierarchical arrangement allows for CSCs to enter periods of quiescence, which can complicate current therapeutic approaches.