epithelium the proliferative burden is met by a stochastically dividing basal epithelium. Upon its transition to the precancerous Barrett's esophagus epithelium, however, a small dedicated stem cell compartment appears that supports proliferation of the epithelium while concomitantly evidence for a stochastically dividing compartment contributing to the maintenance of the tissue disappears. Hence, at least for certain neoplastic tissues, dedicated stem cell compartments maintain and enlarge the size of the transformed compartment The cancer stem cell model The cancer stem cell model, also known as the Hierarchical Model proposes that tumors are hierarchically organized (CSCs lying at the apex (Fig. 3).) Within the cancer population of the tumors there are cancer stem cells (CSC) that are tumorigenic cells and are biologically distinct from other subpopulations They have two defining features: their long-term ability to self-renew and their capacity to differentiate into progeny that is non-tumorigenic but still contributes to the growth of the tumor. This model suggests that only certain subpopulations of cancer stem cells have the ability to drive the progression of cancer, meaning that there are specific (intrinsic) characteristics that can be identified and then targeted to destroy a tumor long-term without the need to battle the whole tumor. Stochastic model In order for a cell to become cancerous it must undergo a significant number of alterations to its DNA sequence. This cell model suggests these mutations could occur to any cell in the body resulting in a cancer. Essentially this theory proposes that all cells have the ability to be tumorigenic making all tumor cells equipotent with the ability to self-renew or differentiate, leading to tumor heterogeneity while others can differentiate into non-CSCs The cell's potential can be influenced by unpredicted genetic or epigenetic factors, resulting in phenotypically diverse cells in both the tumorigenic and non-tumorigenic cells that compose the tumor. According to the "stochastic model" (or "clonal evolution model") every cancer cell in a tumor could gain the ability to self-renew and differentiate to the numerous and heterogeneous lineages of cancer cells that compromise a tumor These mutations could progressively accumulate and enhance the resistance and fitness of cells that allow them to outcompete other tumor cells, better known as the somatic evolution model. The clonal evolution model, which occurs in both the CSC model and stochastic model, postulates that mutant tumor cells with a growth advantage outproliferate others. Cells in the dominant population have a similar