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

Alberto D&apos;Onofrio; Alberto Gandolfi; Sara Gattoni

doi:10.1016/j.physa.2012.07.025

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

Alberto D'Onofrio, Alberto Gandolfi, Sara Gattoni

Istituto Europeo di Oncologia

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	6484-6496
Number of pages	13
Journal	Physica A: Statistical Mechanics and its Applications
Volume	391
Issue number	24
DOIs	https://doi.org/10.1016/j.physa.2012.07.025
Publication status	Published - Dec 15 2012

Keywords

Bounded noises
Chemotherapy
Noise-induced transitions
Norton-Simon hypothesis
Tumor

ASJC Scopus subject areas

Condensed Matter Physics
Statistics and Probability

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