Figure 2.

Cancer evolution and the non-genetic factors involved in treatment resistance. (a) Non-genetic factors can be either heritable (partially) or non-heritable. In case of non-heritable factors, some cells can gain the beneficial state for resistance, but they cannot pass it on to the next generation of cells (top). The heritable states might follow a heritable path, although the degree of heritability is lower than genetic factors. (b) Top: Examples of intrinsic factors causing non-genetic changes in the cell. Only one example of the regulators of cell plasticity is shown (the H3K27 methyltransferase EZH2, the H3K4 methyltransferase MLL, and the lysine demethylase KDM). Bottom: A zoomed-in representation of the cell state changes caused by non-genetic factors. These changes lower the barriers between malignant cells, increasing cell state plasticity.