Concluding Remarks
Tumor cells are complex adaptive systems governed by nonlinear dynamics. Recent studies integrating mathematics, physics, and the biology of such systems have underscored the multifaceted, heterogeneous nature of drug resistance, which evolves dynamically with changes in therapy [34,35]. The results from these thought-provoking theoretical and empirical studies collectively demonstrate that multiple mechanisms regulating phenotypic switching exist even within a given cancer type that can be genetic or non-genetic in nature. Thus, it may be prudent to understand the mechanism involved before considering a therapeutic approach (see Outstanding Questions). For example, including epigenetic modifiers in combination with targeted therapies may help to alter the ability of the cancer cell to switch phenotypes to acquire a drug-resistant state while rendering it more susceptible to adaptive therapy. Although several questions remain (see Outstanding Questions) and a deeper understanding is required, incorporating this new thinking in treatment protocols may help to enhance the precision with which we deliver personalized medicine.
