Triangular Invariant Sets for Containment of Drug Resistance Under Evolutionary Therapy

Abstract Evolutionary therapies regulate heterogeneous populations by altering selective pressures through treatment sequences in cancer and infections. This letter develops an invariant-set framework for treatment-induced containment based on positive triangular invariant sets. For periodically switched systems, sufficient conditions are derived for the existence of such invariant regions. Robustness with respect to mutation is established by showing that the invariant simplex persists under small perturbations of the subsystem matrices. In the two-phenotype case, the analysis yields an explicit mutation threshold that separates regimes in which therapy cycling maintains containment from regimes in which mutation can enable evolutionary escape. Simulations illustrate the geometry of the invariant sets and the role of mutation and dwell time in containment robustness. Competing Interest Statement The authors have declared no competing interest. Footnotes * This material is based on work supported by the National Science Foundation under Grant No. 2315862. (e-mail: esteban{at}uaidaho.edu)