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EXTERNAL CONTROL OF CANCER CELLULAR DYNAMICS USING ADAPTIVE MODEL PREDICTIVE CONTROL

Benjamin Smart, Irene de Cesare, Ludovic Renson, View ORCID ProfileLucia Marucci
doi: https://doi.org/10.1101/2022.03.14.484268
Benjamin Smart
1Department of Mechanical Engineering, Imperial College London, London SW7 1AY, U.K.
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  • For correspondence: b.smart21@imperial.ac.uk
Irene de Cesare
2Department of Engineering Mathematics, University of Bristol, Woodland Road, Bristol BS8 1UB, U.K.
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Ludovic Renson
1Department of Mechanical Engineering, Imperial College London, London SW7 1AY, U.K.
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Lucia Marucci
2Department of Engineering Mathematics, University of Bristol, Woodland Road, Bristol BS8 1UB, U.K.
3BrisSynBio, Life Sciences Building, University of Bristol, Tyndall Avenue, Bristol BS8 1TQ, U.K.
4School of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol BS8 1TD, U.K.
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  • ORCID record for Lucia Marucci
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Abstract

Recent advancements in Cybergenetics have lead to the development of new computational and experimental platforms that enable to robustly steer cellular dynamics by applying external feedback control. Such technologies have never been applied to regulate intracellular dynamics of cancer cells. Here, we show in silico that Adaptive Model Predictive Control (MPC) can effectively be used to steer signalling dynamics in Non-Small Cell Lung Cancer (NSCLC) cells to resemble those of wild-type cells, and to support the design of combination therapies. Our optimisation-based control algorithm enables tailoring the cost function to force the controller to alternate different drugs and/or reduce drug exposure, minimising both drug-induced toxicity and resistance to treatment. Our results pave the way for new cybergenetics experiments in cancer cells for drug combination therapy design.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 11, 2022.
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EXTERNAL CONTROL OF CANCER CELLULAR DYNAMICS USING ADAPTIVE MODEL PREDICTIVE CONTROL
Benjamin Smart, Irene de Cesare, Ludovic Renson, Lucia Marucci
bioRxiv 2022.03.14.484268; doi: https://doi.org/10.1101/2022.03.14.484268
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EXTERNAL CONTROL OF CANCER CELLULAR DYNAMICS USING ADAPTIVE MODEL PREDICTIVE CONTROL
Benjamin Smart, Irene de Cesare, Ludovic Renson, Lucia Marucci
bioRxiv 2022.03.14.484268; doi: https://doi.org/10.1101/2022.03.14.484268

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