Figure 1.

Evolutionary model for the development of drug resistance in cancer cells. (a) Rare pre-existing clones containing resistance mutations (orange) are selected in response to treatment with a specific inhibitor (Inhib.). (b) Alternatively, resistance may arise from tolerant/persister cells capable of surviving in the presence of the inhibitor (light blue and red) and evolve over time to acquire genetic (orange) or non-genetic resistance (green). These cells are selected because of some intrinsic properties (light blue) through non-genetic Darwinian selection, or they can originate more randomly (red), as a direct effect of the inhibitor (Lamarckian induction).