FIGURE 3.

Schematic representation of the hierarchical CSC model of CSCs versus the clonal evolution or stochastic model of tumor cell heterogeneity. The hierarchical model proposes that only limited subpopulations of CSCs have the ability to initiate the development of cancer, with particular (intrinsic) features that could be recognized and targeted to destroy a tumor. In the stochastic model, to form cancerous cells, it is necessary to undergo a substantial series of DNA modifications. In this process, stepwise mutation causes tumor cells. Mutations could happen in any cell, resulting in cancer formation. This concept fundamentally suggests that all cells have the capacity to be tumorigenic with self-renewal or differentiation ability, leading to tumor heterogeneity, and other cells are differentiated as non-CSCs.