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Issue 211: Moving away from MTD dosing requires the treating physician to directly confront the reality of malignant tumors as complex, dynamic, adaptive systems: complex because they consist of multiple cellular and microenvironmental components; dynamic because the components interact with each other through a complex network that changes in space and time; and adaptive because critical elements of the network as well as the network itself can change and adapt to perturbations. Each treatment represents a perturbation of this complex system that elicits equally complex responses—such that optimizing subsequent treatments requires knowledge of the patient, disease, and drug dynamics, as well as the eco-evolutionary responses to the therapy. The image above represents the complexity of tumor growth (adapted from our 2015 Cancer Research paper, Impact of Metabolic Heterogeneity on Tumor Growth, Invasion, and Treatment Outcomes). Read more about the implications of cancer’s dynamic complexity on treatment in this recent blog post.