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Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy

To study quantitatively replicative senescence as a tumor suppressor mechanism, we investigate the distribution of a growing clonal cell population restricted by Hayflick’s limit. We find that in the biologically relevant range of parameters, if the imbalance between cell division and death is moder...

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Detalles Bibliográficos
Autores principales: Rodriguez-Brenes, Ignacio A., Wodarz, Dominik, Komarova, Natalia L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673423/
https://www.ncbi.nlm.nih.gov/pubmed/26647820
http://dx.doi.org/10.1038/srep17660
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author Rodriguez-Brenes, Ignacio A.
Wodarz, Dominik
Komarova, Natalia L.
author_facet Rodriguez-Brenes, Ignacio A.
Wodarz, Dominik
Komarova, Natalia L.
author_sort Rodriguez-Brenes, Ignacio A.
collection PubMed
description To study quantitatively replicative senescence as a tumor suppressor mechanism, we investigate the distribution of a growing clonal cell population restricted by Hayflick’s limit. We find that in the biologically relevant range of parameters, if the imbalance between cell division and death is moderate or low (high death-to-birth ratio), senescence offers significant protection against cancer by halting abnormal cell proliferation at early pre-diagnostic stages of tumor development. We also find that by the time tumors are typically detected, there is a high probability that telomerase is activated, even if the cell of origin was telomerase negative. Hence, the fact that most cancers are positive for telomerase is not necessarily an indication that cancer originated in a telomerase positive cell. Finally, we discuss how the population dynamics of cells can determine the outcomes of anti-telomerase cancer therapies, and provide guidelines on how the model could potentially be applied to develop clinically useful tools to predict the response to treatment by telomerase inhibitors in individual patients.
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spelling pubmed-46734232015-12-14 Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy Rodriguez-Brenes, Ignacio A. Wodarz, Dominik Komarova, Natalia L. Sci Rep Article To study quantitatively replicative senescence as a tumor suppressor mechanism, we investigate the distribution of a growing clonal cell population restricted by Hayflick’s limit. We find that in the biologically relevant range of parameters, if the imbalance between cell division and death is moderate or low (high death-to-birth ratio), senescence offers significant protection against cancer by halting abnormal cell proliferation at early pre-diagnostic stages of tumor development. We also find that by the time tumors are typically detected, there is a high probability that telomerase is activated, even if the cell of origin was telomerase negative. Hence, the fact that most cancers are positive for telomerase is not necessarily an indication that cancer originated in a telomerase positive cell. Finally, we discuss how the population dynamics of cells can determine the outcomes of anti-telomerase cancer therapies, and provide guidelines on how the model could potentially be applied to develop clinically useful tools to predict the response to treatment by telomerase inhibitors in individual patients. Nature Publishing Group 2015-12-09 /pmc/articles/PMC4673423/ /pubmed/26647820 http://dx.doi.org/10.1038/srep17660 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Rodriguez-Brenes, Ignacio A.
Wodarz, Dominik
Komarova, Natalia L.
Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy
title Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy
title_full Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy
title_fullStr Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy
title_full_unstemmed Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy
title_short Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy
title_sort quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673423/
https://www.ncbi.nlm.nih.gov/pubmed/26647820
http://dx.doi.org/10.1038/srep17660
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