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Bounded Stochastic Perturbations May Induce Nongenetic Resistance to Antitumor Chemotherapy

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Bounded Noises in Physics, Biology, and Engineering

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Abstract

Recent 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.

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Notes

  1. 1.

    Indeed, the noise-induced transitions theory usually refers to transitions to/from multimodality in steady state probability densities.

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Acknowledgments

The work of A. d’Onofrio was conducted within the framework of the EU Integrated Projects “Advancing Clinico-Genomic Trials on Cancer ACGT” and “P-Medicine.” This work was also partially supported by MIUR-Italy, PRIN 2008RSZPYY.

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Authors and Affiliations

  1. Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, I20141, Milan, Italy

    Alberto d’Onofrio

  2. Istituto di Analisi dei Sistemi ed Informatica “A. Ruberti” - CNR, Viale Manzoni 30, I00185, Roma, Italy

    Alberto Gandolfi

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  1. Alberto d’Onofrio
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  2. Alberto Gandolfi
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Correspondence to Alberto d’Onofrio .

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Editors and Affiliations

  1. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

    Alberto d'Onofrio

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d’Onofrio, A., Gandolfi, A. (2013). Bounded Stochastic Perturbations May Induce Nongenetic Resistance to Antitumor Chemotherapy. In: d'Onofrio, A. (eds) Bounded Noises in Physics, Biology, and Engineering. Modeling and Simulation in Science, Engineering and Technology. Birkhäuser, New York, NY. https://doi.org/10.1007/978-1-4614-7385-5_11

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