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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2021
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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). |
format | Online Article Text |
id | pubmed-8479343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
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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