Figure 3. Therapeutic approach to glioblastoma stem cell adaptation and heterogeneity.

i) Classical therapeutic approaches often spare the GSC population or target individual components of the tumor landscape – e.g. tumor vasculature or rapidly dividing cell populations. This generates new attractor states along with the older untreated states and allows for the tumor to evolve and repopulate. ii) The attractor state model implies that effective therapy will require a combinatorial approach. The first treatment bottlenecks tumor adaptation by applying an initial stimulus that drives cells towards one state, and the second intervention is targeted at the resulting specific cellular state. Abbreviations: GSC, glioblastoma stem cell