Antifragile Control Systems: The Case of an Anti-Symmetric Network Model of the Tumor-Immune-Drug Interactions

A therapy's outcome is determined by a tumor's response to treatment which, in turn, depends on multiple factors such as the severity of the disease and the strength of the patient's immune response. Gold standard cancer therapies are in most cases fragile when sought to break the ties to either tumor kill ratio or patient toxicity. Lately, research has shown that cancer therapy can be at its most robust when handling adaptive drug resistance and immune escape patterns developed by evolving tumors. This is due to the stochastic and volatile nature of the interactions, at the tumor environment level, tissue vasculature, and immune landscape, induced by drugs. Herein, we explore the path toward antifragile therapy control, that generates treatment schemes that are not fragile but go beyond robustness. More precisely, we describe the first instantiation of a control-theoretic method to make therapy schemes cope with the systemic variability in the tumor-immune-drug interactions and gain more tumor kills with less patient toxicity. Considering the anti-symmetric interactions within a model of the tumor-immune-drug network, we introduce the antifragile control framework that demonstrates promising results in simulation. We evaluate our control strategy against state-of-the-art therapy schemes in various experiments and discuss the insights we gained on the potential that antifragile control could have in treatment design in clinical settings.