Studying Bone Remodelling and Tumour Growth for Therapy Predictive Control

Bone remodelling consists of cycles of bone resorption and formation executed mainly by osteoclasts and osteoblasts. Healthy bone remodelling is disrupted by diseases such as Multiple Myeloma and bone metastatic diseases. In this paper, a simple mathematical model with differential equations, which...

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Main Authors: Raquel Miranda, Susana Vinga, Duarte Valério
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Mathematics
Subjects:
Online Access:https://www.mdpi.com/2227-7390/8/5/679
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author Raquel Miranda
Susana Vinga
Duarte Valério
author_facet Raquel Miranda
Susana Vinga
Duarte Valério
author_sort Raquel Miranda
collection DOAJ
description Bone remodelling consists of cycles of bone resorption and formation executed mainly by osteoclasts and osteoblasts. Healthy bone remodelling is disrupted by diseases such as Multiple Myeloma and bone metastatic diseases. In this paper, a simple mathematical model with differential equations, which takes into account the evolution of osteoclasts, osteoblasts, bone mass and bone metastasis growth, is improved with a pharmacokinetic and pharmacodynamic (PK/PD) scheme of the drugs denosumab, bisphosphonates, proteasome inhibitors and paclitaxel. The major novelty is the inclusion of drug resistance phenomena, which resulted in two variations of the model, corresponding to different paradigms of the origin and development of the tumourous cell resistance condition. These models are then used as basis for an optimization of the drug dose applied, paving the way for personalized medicine. A Nonlinear Model Predictive Control scheme is used, which takes advantage of the convenient properties of a suggested adaptive and democratic variant of Particle Swarm Optimization. Drug prescriptions obtained in this way provide useful insights into dose administration strategies. They also show how results may change depending on which of the two very different paradigms of drug resistance is used to model the behaviour of the tumour.
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spelling doaj.art-15f8cdea514844d89e5f6bd31104a5392023-11-19T23:12:01ZengMDPI AGMathematics2227-73902020-05-018567910.3390/math8050679Studying Bone Remodelling and Tumour Growth for Therapy Predictive ControlRaquel Miranda0Susana Vinga1Duarte Valério2IDMEC, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, PortugalIDMEC, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, PortugalIDMEC, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, PortugalBone remodelling consists of cycles of bone resorption and formation executed mainly by osteoclasts and osteoblasts. Healthy bone remodelling is disrupted by diseases such as Multiple Myeloma and bone metastatic diseases. In this paper, a simple mathematical model with differential equations, which takes into account the evolution of osteoclasts, osteoblasts, bone mass and bone metastasis growth, is improved with a pharmacokinetic and pharmacodynamic (PK/PD) scheme of the drugs denosumab, bisphosphonates, proteasome inhibitors and paclitaxel. The major novelty is the inclusion of drug resistance phenomena, which resulted in two variations of the model, corresponding to different paradigms of the origin and development of the tumourous cell resistance condition. These models are then used as basis for an optimization of the drug dose applied, paving the way for personalized medicine. A Nonlinear Model Predictive Control scheme is used, which takes advantage of the convenient properties of a suggested adaptive and democratic variant of Particle Swarm Optimization. Drug prescriptions obtained in this way provide useful insights into dose administration strategies. They also show how results may change depending on which of the two very different paradigms of drug resistance is used to model the behaviour of the tumour.https://www.mdpi.com/2227-7390/8/5/679bone remodellingPK/PDbone metastasismodel predictive controlparticle swarm optimization
spellingShingle Raquel Miranda
Susana Vinga
Duarte Valério
Studying Bone Remodelling and Tumour Growth for Therapy Predictive Control
Mathematics
bone remodelling
PK/PD
bone metastasis
model predictive control
particle swarm optimization
title Studying Bone Remodelling and Tumour Growth for Therapy Predictive Control
title_full Studying Bone Remodelling and Tumour Growth for Therapy Predictive Control
title_fullStr Studying Bone Remodelling and Tumour Growth for Therapy Predictive Control
title_full_unstemmed Studying Bone Remodelling and Tumour Growth for Therapy Predictive Control
title_short Studying Bone Remodelling and Tumour Growth for Therapy Predictive Control
title_sort studying bone remodelling and tumour growth for therapy predictive control
topic bone remodelling
PK/PD
bone metastasis
model predictive control
particle swarm optimization
url https://www.mdpi.com/2227-7390/8/5/679
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