The Norton–Simon hypothesis and the onset of non-genetic resistance to chemotherapy induced by stochastic fluctuations

By studying a simple but realistic biophysical model of tumor growth in the presence of a constant continuous chemotherapy, we show that if an extended Norton–Simon hypothesis holds, the system may have multiple equilibria. Thus, the stochastic bounded fluctuations that affect both the tumor carrying capacity and/or the drug pharmacodynamics (and/or the drug pharmacokinetics) may cause the transition from a small equilibrium to a far larger one, not compatible with the life of the host. In particular, we mainly investigated the effects of fluctuations that involve parameters nonlinearly affecting the deterministic model. We propose to frame the above phenomena as a new and non-genetic kind of resistance to chemotherapy.