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Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer
In the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723267/ https://www.ncbi.nlm.nih.gov/pubmed/33290430 http://dx.doi.org/10.1371/journal.pone.0243386 |
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author | Cunningham, Jessica Thuijsman, Frank Peeters, Ralf Viossat, Yannick Brown, Joel Gatenby, Robert Staňková, Kateřina |
author_facet | Cunningham, Jessica Thuijsman, Frank Peeters, Ralf Viossat, Yannick Brown, Joel Gatenby, Robert Staňková, Kateřina |
author_sort | Cunningham, Jessica |
collection | PubMed |
description | In the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what is coined as an ‘evolutionary stable therapy’, within the context of the mathematical model that has been used to inform the first adaptive therapy clinical trial of mCRPC. The objective of this therapy is to maintain a stable polymorphic tumor heterogeneity of sensitive and resistant cells to therapy in order to prolong treatment efficacy and progression free survival. Optimal control analysis shows that an increasing dose titration protocol, a very common clinical dosing process, can achieve tumor stabilization for a wide range of potential initial tumor compositions and volumes. Furthermore, larger tumor volumes may counter intuitively be more likely to be stabilized if sensitive cells dominate the tumor composition at time of initial treatment, suggesting a delay of initial treatment could prove beneficial. While it remains uncertain if metastatic disease in humans has the properties that allow it to be truly stabilized, the benefits of a dose titration protocol warrant additional pre-clinical and clinical investigations. |
format | Online Article Text |
id | pubmed-7723267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-77232672020-12-16 Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer Cunningham, Jessica Thuijsman, Frank Peeters, Ralf Viossat, Yannick Brown, Joel Gatenby, Robert Staňková, Kateřina PLoS One Research Article In the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what is coined as an ‘evolutionary stable therapy’, within the context of the mathematical model that has been used to inform the first adaptive therapy clinical trial of mCRPC. The objective of this therapy is to maintain a stable polymorphic tumor heterogeneity of sensitive and resistant cells to therapy in order to prolong treatment efficacy and progression free survival. Optimal control analysis shows that an increasing dose titration protocol, a very common clinical dosing process, can achieve tumor stabilization for a wide range of potential initial tumor compositions and volumes. Furthermore, larger tumor volumes may counter intuitively be more likely to be stabilized if sensitive cells dominate the tumor composition at time of initial treatment, suggesting a delay of initial treatment could prove beneficial. While it remains uncertain if metastatic disease in humans has the properties that allow it to be truly stabilized, the benefits of a dose titration protocol warrant additional pre-clinical and clinical investigations. Public Library of Science 2020-12-08 /pmc/articles/PMC7723267/ /pubmed/33290430 http://dx.doi.org/10.1371/journal.pone.0243386 Text en © 2020 Cunningham et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Cunningham, Jessica Thuijsman, Frank Peeters, Ralf Viossat, Yannick Brown, Joel Gatenby, Robert Staňková, Kateřina Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer |
title | Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer |
title_full | Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer |
title_fullStr | Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer |
title_full_unstemmed | Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer |
title_short | Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer |
title_sort | optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723267/ https://www.ncbi.nlm.nih.gov/pubmed/33290430 http://dx.doi.org/10.1371/journal.pone.0243386 |
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