The role of memory in non-genetic inheritance and its impact on cancer treatment resistance.

Intra-tumour heterogeneity is a leading cause of treatment failure and disease progression in cancer. While genetic mutations have long been accepted as a primary mechanism of generating this heterogeneity, the role of phenotypic plasticity is becoming increasingly apparent as a driver of intra-tumo...

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Autores principales:	Tyler Cassidy, Daniel Nichol, Mark Robertson-Tessi, Morgan Craig, Alexander R A Anderson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d6c120fed11b4ebeb8bb0479a0ce7d3f
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spelling	oai:doaj.org-article:d6c120fed11b4ebeb8bb0479a0ce7d3f2021-12-02T19:58:00ZThe role of memory in non-genetic inheritance and its impact on cancer treatment resistance.1553-734X1553-735810.1371/journal.pcbi.1009348https://doaj.org/article/d6c120fed11b4ebeb8bb0479a0ce7d3f2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009348https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Intra-tumour heterogeneity is a leading cause of treatment failure and disease progression in cancer. While genetic mutations have long been accepted as a primary mechanism of generating this heterogeneity, the role of phenotypic plasticity is becoming increasingly apparent as a driver of intra-tumour heterogeneity. Consequently, understanding the role of this plasticity in treatment resistance and failure is a key component of improving cancer therapy. We develop a mathematical model of stochastic phenotype switching that tracks the evolution of drug-sensitive and drug-tolerant subpopulations to clarify the role of phenotype switching on population growth rates and tumour persistence. By including cytotoxic therapy in the model, we show that, depending on the strategy of the drug-tolerant subpopulation, stochastic phenotype switching can lead to either transient or permanent drug resistance. We study the role of phenotypic heterogeneity in a drug-resistant, genetically homogeneous population of non-small cell lung cancer cells to derive a rational treatment schedule that drives population extinction and avoids competitive release of the drug-tolerant sub-population. This model-informed therapeutic schedule results in increased treatment efficacy when compared against periodic therapy, and, most importantly, sustained tumour decay without the development of resistance.Tyler CassidyDaniel NicholMark Robertson-TessiMorgan CraigAlexander R A AndersonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 8, p e1009348 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Tyler Cassidy Daniel Nichol Mark Robertson-Tessi Morgan Craig Alexander R A Anderson The role of memory in non-genetic inheritance and its impact on cancer treatment resistance.
description	Intra-tumour heterogeneity is a leading cause of treatment failure and disease progression in cancer. While genetic mutations have long been accepted as a primary mechanism of generating this heterogeneity, the role of phenotypic plasticity is becoming increasingly apparent as a driver of intra-tumour heterogeneity. Consequently, understanding the role of this plasticity in treatment resistance and failure is a key component of improving cancer therapy. We develop a mathematical model of stochastic phenotype switching that tracks the evolution of drug-sensitive and drug-tolerant subpopulations to clarify the role of phenotype switching on population growth rates and tumour persistence. By including cytotoxic therapy in the model, we show that, depending on the strategy of the drug-tolerant subpopulation, stochastic phenotype switching can lead to either transient or permanent drug resistance. We study the role of phenotypic heterogeneity in a drug-resistant, genetically homogeneous population of non-small cell lung cancer cells to derive a rational treatment schedule that drives population extinction and avoids competitive release of the drug-tolerant sub-population. This model-informed therapeutic schedule results in increased treatment efficacy when compared against periodic therapy, and, most importantly, sustained tumour decay without the development of resistance.
format	article
author	Tyler Cassidy Daniel Nichol Mark Robertson-Tessi Morgan Craig Alexander R A Anderson
author_facet	Tyler Cassidy Daniel Nichol Mark Robertson-Tessi Morgan Craig Alexander R A Anderson
author_sort	Tyler Cassidy
title	The role of memory in non-genetic inheritance and its impact on cancer treatment resistance.
title_short	The role of memory in non-genetic inheritance and its impact on cancer treatment resistance.
title_full	The role of memory in non-genetic inheritance and its impact on cancer treatment resistance.
title_fullStr	The role of memory in non-genetic inheritance and its impact on cancer treatment resistance.
title_full_unstemmed	The role of memory in non-genetic inheritance and its impact on cancer treatment resistance.
title_sort	role of memory in non-genetic inheritance and its impact on cancer treatment resistance.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d6c120fed11b4ebeb8bb0479a0ce7d3f
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The role of memory in non-genetic inheritance and its impact on cancer treatment resistance.

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