Created by: Erida Gjini, Kevin Wood
Issue 181: The combined effects of mutational constraints, collateral effects (cross resistance or collateral sensitivity), and drug interactions shape the dynamics of multi-drug resistance. In our recent paper, we show that these processes can be integrated via a Price Equation whose terms encode statistical properties of resistance mutants, geometric features of the two-drug response surface in ancestral cells, and mutational constraints that limit the available pathways for sequential mutations. In this model, growth adaptation follows a type of weighted gradient dynamics where the underlying landscape is determined by the drug interaction, while the collateral effects and mutational pathways constrain motion on that landscape. To learn more, see our paper here.