Figure 2.

Proposed Generative Hierarchies for Cancer and the Effect of Inflammation. A depiction of an example of the multi-scale effects of inflammation on the development and subsequent behavior of a tumor, incorporating evolutionary and selection effects across the scales from DNA to cellular populations. This paradigm posits that increased and accumulating genetic damage in an inflammatory milieu leads to a progressive loss of the cellular and molecular control structures that govern stable multi-cellular organization. The loss of these control structures in the tumor leads a more “colony-like” behavior, where the genetic plasticity of the increasingly disordered tumor cells provides a potential selection benefit when subjected to therapeutic interventions, akin to how microbial colonies utilize genetic heterogeneity as an adaptive strategy (as seen in antibiotic resistance). The incorporation of these concepts into a multi-scale computational model allows the exploration of various fundamental processes and behaviors involved in this hypothesis. Reprinted with permission from ref. 81.