Figure 2.

Models of tumor growth. The cancer stem cell model (A) suggests a hierarchy of cells in which only a small subset of tumorigenic cells exists. These tumor-forming cancer stem cells (CSC) have self-renewal capacity (SR) and potential to differentiate into non-tumorigenic cells. As a consequence, a neoplasm contains cancer stem cells that feed the abnormal growth of the tissue, cells that divide a few times before they differentiate into specialized tumor cells, and inactive tumor cells. The clonal evolution theory (B) that is a stochastic model suggests that a tumor is the result of a single mutated somatic cell that acquires a highly proliferative phenotype and accumulates additional mutations during repeated divisions. There is no hierarchy during tumorigenesis and the resulting subpopulations have different potential to grow and divide. The resulting subclones can independently choose between self-renewal and differentiation and during time the tumor environment create dominant cell variants that have acquired growth advantages. While in the cancer stem cell model individual CSCs are therapeutic targets, individual somatic cells with unwanted reproductive or survival properties must be tackled therapeutically according to the clonal evolution model.