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Mathematical model of STAT signalling pathways in cancer development and optimal control approaches

In various diseases, the STAT family display various cellular controls over various challenges faced by the immune system and cell death programs. In this study, we investigate how an intracellular signalling network (STAT1, STAT3, Bcl-2 and BAX) regulates important cellular states, either anti-apop...

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Autores principales: Lee, Jonggul, Lee, Donggu, Kim, Yangjin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479343/
https://www.ncbi.nlm.nih.gov/pubmed/34631119
http://dx.doi.org/10.1098/rsos.210594
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author Lee, Jonggul
Lee, Donggu
Kim, Yangjin
author_facet Lee, Jonggul
Lee, Donggu
Kim, Yangjin
author_sort Lee, Jonggul
collection PubMed
description In various diseases, the STAT family display various cellular controls over various challenges faced by the immune system and cell death programs. In this study, we investigate how an intracellular signalling network (STAT1, STAT3, Bcl-2 and BAX) regulates important cellular states, either anti-apoptosis or apoptosis of cancer cells. We adapt a mathematical framework to illustrate how the signalling network can generate a bi-stability condition so that it will induce either apoptosis or anti-apoptosis status of tumour cells. Then, we use this model to develop several anti-tumour strategies including IFN-β infusion. The roles of JAK-STATs signalling in regulation of the cell death program in cancer cells and tumour growth are poorly understood. The mathematical model unveils the structure and functions of the intracellular signalling and cellular outcomes of the anti-tumour drugs in the presence of IFN-β and JAK stimuli. We identify the best injection order of IFN-β and DDP among many possible combinations, which may suggest better infusion strategies of multiple anti-cancer agents at clinics. We finally use an optimal control theory in order to maximize anti-tumour efficacy and minimize administrative costs. In particular, we minimize tumour volume and maximize the apoptotic potential by minimizing the Bcl-2 concentration and maximizing the BAX level while minimizing total injection amount of both IFN-β and JAK2 inhibitors (DDP).
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spelling pubmed-84793432021-10-08 Mathematical model of STAT signalling pathways in cancer development and optimal control approaches Lee, Jonggul Lee, Donggu Kim, Yangjin R Soc Open Sci Mathematics In various diseases, the STAT family display various cellular controls over various challenges faced by the immune system and cell death programs. In this study, we investigate how an intracellular signalling network (STAT1, STAT3, Bcl-2 and BAX) regulates important cellular states, either anti-apoptosis or apoptosis of cancer cells. We adapt a mathematical framework to illustrate how the signalling network can generate a bi-stability condition so that it will induce either apoptosis or anti-apoptosis status of tumour cells. Then, we use this model to develop several anti-tumour strategies including IFN-β infusion. The roles of JAK-STATs signalling in regulation of the cell death program in cancer cells and tumour growth are poorly understood. The mathematical model unveils the structure and functions of the intracellular signalling and cellular outcomes of the anti-tumour drugs in the presence of IFN-β and JAK stimuli. We identify the best injection order of IFN-β and DDP among many possible combinations, which may suggest better infusion strategies of multiple anti-cancer agents at clinics. We finally use an optimal control theory in order to maximize anti-tumour efficacy and minimize administrative costs. In particular, we minimize tumour volume and maximize the apoptotic potential by minimizing the Bcl-2 concentration and maximizing the BAX level while minimizing total injection amount of both IFN-β and JAK2 inhibitors (DDP). The Royal Society 2021-09-29 /pmc/articles/PMC8479343/ /pubmed/34631119 http://dx.doi.org/10.1098/rsos.210594 Text en © 2021 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Mathematics
Lee, Jonggul
Lee, Donggu
Kim, Yangjin
Mathematical model of STAT signalling pathways in cancer development and optimal control approaches
title Mathematical model of STAT signalling pathways in cancer development and optimal control approaches
title_full Mathematical model of STAT signalling pathways in cancer development and optimal control approaches
title_fullStr Mathematical model of STAT signalling pathways in cancer development and optimal control approaches
title_full_unstemmed Mathematical model of STAT signalling pathways in cancer development and optimal control approaches
title_short Mathematical model of STAT signalling pathways in cancer development and optimal control approaches
title_sort mathematical model of stat signalling pathways in cancer development and optimal control approaches
topic Mathematics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479343/
https://www.ncbi.nlm.nih.gov/pubmed/34631119
http://dx.doi.org/10.1098/rsos.210594
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