Figure 2

Schematic representation of how treatment affects tumor heterogeneity. A population of cells with various levels of competitive ability show differential responses to treatment, depending on the strength of the selection pressure imposed by the treatment and the heterogeneity present in the population. Treatment providing weak selection pressure (a,b) is expected to result in a balanced regrowth of the population that continues to progress when the heterogeneity is low (a); however, a reduction in population size offers opportunity for colonization and preferential growth of any aggressive clones that may be present in more heterogeneous populations (b). A strong selection pressure (c,d) will not allow clones with low-level tolerance to persist. Therefore, a homogeneous population that does not harbor a resistance mutation will respond well to strong treatment and population sizes are expected to dramatically reduce (c). However, heterogeneous populations are more likely to harbor cells with a mutation that confers resistance, and under strong selection these cells will be the only ones to survive. The subsequent population will no longer respond to treatment (d). In all cases, cells that survive treatment can acquire further mutations, this will be particularly important for resistant populations and the propensity for multidrug resistance.