Closed-loop control of tumor growth by means of anti-angiogenic administration

A tumor growth model accounting for angiogenic stimulation and inhibition is here considered, and a closed-loop control law is presented with the aim of tumor volume reduction by means of anti-angiogenic administration. To this end the output-feedback linearization theory is exploited, with the feed...

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Main Authors: Filippo Cacace, Valerio Cusimano, Alfredo Germani, Pasquale Palumbo, Federico Papa
Format: Article
Language:English
Published: AIMS Press 2018-07-01
Series:Mathematical Biosciences and Engineering
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Online Access:https://www.aimspress.com/article/doi/10.3934/mbe.2018037
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author Filippo Cacace
Valerio Cusimano
Alfredo Germani
Pasquale Palumbo
Federico Papa
author_facet Filippo Cacace
Valerio Cusimano
Alfredo Germani
Pasquale Palumbo
Federico Papa
author_sort Filippo Cacace
collection DOAJ
description A tumor growth model accounting for angiogenic stimulation and inhibition is here considered, and a closed-loop control law is presented with the aim of tumor volume reduction by means of anti-angiogenic administration. To this end the output-feedback linearization theory is exploited, with the feedback designed on the basis of a state observer for nonlinear systems. Measurements are supposed to be acquired at discrete sampling times, and a novel theoretical development in the area of time-delay systems is applied in order to derive a continuous-time observer in spite of the presence of sampled measurements. The overall control scheme allows to set independently the control and the observer parameters thanks to the structural properties of the tumor growth model. Simulations are carried out in order to mimic a real experimental framework on mice. These results seem extremely promising: they provide very good performances according to the measurements sampling interval suggested by the experimental literature, and show a noticeable level of robustness against the observer initial estimate, as well as against the uncertainties affecting the model parameters.
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spelling doaj-art-a1d8eada54ca4e10b08aacdb1f441cb12025-01-24T02:40:56ZengAIMS PressMathematical Biosciences and Engineering1551-00182018-07-0115482783910.3934/mbe.2018037Closed-loop control of tumor growth by means of anti-angiogenic administrationFilippo Cacace0Valerio Cusimano1Alfredo Germani2Pasquale Palumbo3Federico Papa4Università Campus Bio-medico di Roma, Roma, Via Álvaro del Portillo 21, 00128, ItalyUniversità Campus Bio-medico di Roma, Roma, Via Álvaro del Portillo 21, 00128, ItalyUniversità Campus Bio-medico di Roma, Roma, Via Álvaro del Portillo 21, 00128, ItalyUniversità Campus Bio-medico di Roma, Roma, Via Álvaro del Portillo 21, 00128, ItalyUniversità Campus Bio-medico di Roma, Roma, Via Álvaro del Portillo 21, 00128, ItalyA tumor growth model accounting for angiogenic stimulation and inhibition is here considered, and a closed-loop control law is presented with the aim of tumor volume reduction by means of anti-angiogenic administration. To this end the output-feedback linearization theory is exploited, with the feedback designed on the basis of a state observer for nonlinear systems. Measurements are supposed to be acquired at discrete sampling times, and a novel theoretical development in the area of time-delay systems is applied in order to derive a continuous-time observer in spite of the presence of sampled measurements. The overall control scheme allows to set independently the control and the observer parameters thanks to the structural properties of the tumor growth model. Simulations are carried out in order to mimic a real experimental framework on mice. These results seem extremely promising: they provide very good performances according to the measurements sampling interval suggested by the experimental literature, and show a noticeable level of robustness against the observer initial estimate, as well as against the uncertainties affecting the model parameters.https://www.aimspress.com/article/doi/10.3934/mbe.2018037general biology and biomathematicsnonlinear systemsdiscrete-time systemsfeedback controlobservability
spellingShingle Filippo Cacace
Valerio Cusimano
Alfredo Germani
Pasquale Palumbo
Federico Papa
Closed-loop control of tumor growth by means of anti-angiogenic administration
Mathematical Biosciences and Engineering
general biology and biomathematics
nonlinear systems
discrete-time systems
feedback control
observability
title Closed-loop control of tumor growth by means of anti-angiogenic administration
title_full Closed-loop control of tumor growth by means of anti-angiogenic administration
title_fullStr Closed-loop control of tumor growth by means of anti-angiogenic administration
title_full_unstemmed Closed-loop control of tumor growth by means of anti-angiogenic administration
title_short Closed-loop control of tumor growth by means of anti-angiogenic administration
title_sort closed loop control of tumor growth by means of anti angiogenic administration
topic general biology and biomathematics
nonlinear systems
discrete-time systems
feedback control
observability
url https://www.aimspress.com/article/doi/10.3934/mbe.2018037
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AT valeriocusimano closedloopcontroloftumorgrowthbymeansofantiangiogenicadministration
AT alfredogermani closedloopcontroloftumorgrowthbymeansofantiangiogenicadministration
AT pasqualepalumbo closedloopcontroloftumorgrowthbymeansofantiangiogenicadministration
AT federicopapa closedloopcontroloftumorgrowthbymeansofantiangiogenicadministration