Bounded Stochastic Perturbations May Induce Nongenetic Resistance to Antitumor Chemotherapy

2Recent deterministic models suggest that for solid and nonsolid tumors the delivery of constant continuous infusion therapy may induce multistability in the tumor size. In other words, therapy, when not able to produce tumor eradication, may at least lead to a small equilibrium that coexists with a far larger one. However, bounded stochastic fluctuations affect the drug concentration profiles, as well as the actual delivery scheduling, and other factors essential to tumor viability (e.g., proangiogenic factors). Through numerical simulations, and under various regimens of delivery, we show that the tumor volume during therapy can undergo transitions to the higher equilibrium value induced by a bounded noise perturbing various biologically well-defined parameters. Finally, we propose to interpretate the above phenomena as a new kind of resistance to chemotherapy.nonemixedD'ONOFRIO A; GANDOLFI AD'Onofrio, A; Gandolfi,