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

Abstract

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.

Antifragile Control Systems: The Case of Mobile Robot Trajectory Tracking Under Uncertainty and Volatility

“…1). In this work, we propose an alternative controller synthesis mechanism for mobile robots, extending the work in [9], based on the novel antifragile control framework introduced in [6] for therapy control and extended in [7] to traffic control. To provide an intuitive understanding of the antifragile control framework, we illustrate the fragility-robustness-antifragility spectrum inFig.…”

“…The work of [6] and [7] was an attempt to cast the control design in geometric control and Riemannian geometry. This made it possible for us to operate in a coordinate-free setting by depending on a manifold's embedding into an expanded dynamical space, which allowed for the construction of control laws that were more straightforward and suitable for manifolds with curvature.…”

“…This stage is rather application-dependent, so we'll explain why we chose the trajectory tracking problem we did. We start from the canonical form of a sliding manifold s depending on system state dynamics x (see (6) for the general dynamical system formulation) in (8).…”

Second-order effects of chemotherapy pharmacodynamics and pharmacokinetics on tumor regression and cachexia

“…Conversely, if the underlying dose response is concave, uneven dosing is optimal: a high dose followed by a low dose. Others have followed similar approaches in applying antifragile theory to cancer applications including immune-tumor interactions 9 , biological boolean networks 10 , molecular biology and evolution 11 .…”