Atorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.

Acute administration of trastuzumab (TZB) may induce various forms of cognitive impairment. These cancer-related cognitive changes (CRCC) are regulated by an adverse biological process involving cancer stem cells (CSCs) and IL-6. Recent studies have reported that atorvastatin (ATV) may change the dy...

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Autores principales:	Junho Lee, Jin Su Kim, Yangjin Kim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/028a3007b803456891466122a1135112
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spelling	oai:doaj.org-article:028a3007b803456891466122a11351122021-12-02T19:57:28ZAtorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.1553-734X1553-735810.1371/journal.pcbi.1009457https://doaj.org/article/028a3007b803456891466122a11351122021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009457https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Acute administration of trastuzumab (TZB) may induce various forms of cognitive impairment. These cancer-related cognitive changes (CRCC) are regulated by an adverse biological process involving cancer stem cells (CSCs) and IL-6. Recent studies have reported that atorvastatin (ATV) may change the dynamic of cognitive impairment in a combination (TZB+ATV) therapy. In this study, we investigate the mutual interactions between cancer stem cells and the tumor cells that facilitate cognitive impairment during long term TZB therapy by developing a mathematical model that involves IL-6 and the key apoptotic regulation. These include the densities of tumor cells and CSCs, and the concentrations of intracellular signaling molecules (NFκB, Bcl-2, BAX). We apply the mathematical model to a single or combination (ATV+TZB) therapy used in the experiments to demonstrate that the CSCs can enhance CRCC by secreting IL-6 and ATV may interfere the whole regulation. We show that the model can both reproduce the major experimental observation on onset and prevention of CRCC, and suggest several important predictions to guide future experiments with the goal of the development of new anti-tumor and anti-CRCC strategies. Moreover, using this model, we investigate the fundamental mechanism of onset of cognitive impairment in TZB-treated patients and the impact of alternating therapies on the anti-tumor efficacy and intracellular response to different treatment schedules.Junho LeeJin Su KimYangjin KimPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 10, p e1009457 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Junho Lee Jin Su Kim Yangjin Kim Atorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.
description	Acute administration of trastuzumab (TZB) may induce various forms of cognitive impairment. These cancer-related cognitive changes (CRCC) are regulated by an adverse biological process involving cancer stem cells (CSCs) and IL-6. Recent studies have reported that atorvastatin (ATV) may change the dynamic of cognitive impairment in a combination (TZB+ATV) therapy. In this study, we investigate the mutual interactions between cancer stem cells and the tumor cells that facilitate cognitive impairment during long term TZB therapy by developing a mathematical model that involves IL-6 and the key apoptotic regulation. These include the densities of tumor cells and CSCs, and the concentrations of intracellular signaling molecules (NFκB, Bcl-2, BAX). We apply the mathematical model to a single or combination (ATV+TZB) therapy used in the experiments to demonstrate that the CSCs can enhance CRCC by secreting IL-6 and ATV may interfere the whole regulation. We show that the model can both reproduce the major experimental observation on onset and prevention of CRCC, and suggest several important predictions to guide future experiments with the goal of the development of new anti-tumor and anti-CRCC strategies. Moreover, using this model, we investigate the fundamental mechanism of onset of cognitive impairment in TZB-treated patients and the impact of alternating therapies on the anti-tumor efficacy and intracellular response to different treatment schedules.
format	article
author	Junho Lee Jin Su Kim Yangjin Kim
author_facet	Junho Lee Jin Su Kim Yangjin Kim
author_sort	Junho Lee
title	Atorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.
title_short	Atorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.
title_full	Atorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.
title_fullStr	Atorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.
title_full_unstemmed	Atorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.
title_sort	atorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/028a3007b803456891466122a1135112
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Atorvastatin-mediated rescue of cancer-related cognitive changes in combined anticancer therapies.

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