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Anti-angiogenic drug scheduling optimisation with application to colorectal cancer
Bevacizumab (bvz) is a first choice anti-angiogenic drug in oncology and is primarily administered in combination with chemotherapy. It has been hypothesized that anti-angiogenic drugs enhance efficacy of cytotoxic drugs by “normalizing” abnormal tumor vessels and improving drug penetration. Neverth...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060139/ https://www.ncbi.nlm.nih.gov/pubmed/30046049 http://dx.doi.org/10.1038/s41598-018-29318-5 |
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author | Sturrock, M. Miller, I. S. Kang, G. Hannis Arba’ie, N. O’Farrell, A. C. Barat, A. Marston, G. Coletta, P. L. Byrne, A. T. Prehn, J. H. |
author_facet | Sturrock, M. Miller, I. S. Kang, G. Hannis Arba’ie, N. O’Farrell, A. C. Barat, A. Marston, G. Coletta, P. L. Byrne, A. T. Prehn, J. H. |
author_sort | Sturrock, M. |
collection | PubMed |
description | Bevacizumab (bvz) is a first choice anti-angiogenic drug in oncology and is primarily administered in combination with chemotherapy. It has been hypothesized that anti-angiogenic drugs enhance efficacy of cytotoxic drugs by “normalizing” abnormal tumor vessels and improving drug penetration. Nevertheless, the clinical relevance of this phenomenon is still unclear with several studies over recent years suggesting an opposing relationship. Herein, we sought to develop a new computational tool to interrogate anti-angiogenic drug scheduling with particular application in the setting of colorectal cancer (CRC). Specifically, we have employed a mathematical model of vascular tumour growth which interrogates the impact of anti-angiogenic treatment and chemotherapeutic treatment on tumour volume. Model predictions were validated using CRC xenografts which underwent treatment with a clinically relevant combinatorial anti-angiogenic regimen. Bayesian model selection revealed the most appropriate term for capturing the effect of treatments on the tumour size, and provided insights into a switch-like dependence of FOLFOX delivery on the tumour vasculature. Our experimental data and mathematical model suggest that delivering chemotherapy prior to bvz may be optimal in the colorectal cancer setting. |
format | Online Article Text |
id | pubmed-6060139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60601392018-07-31 Anti-angiogenic drug scheduling optimisation with application to colorectal cancer Sturrock, M. Miller, I. S. Kang, G. Hannis Arba’ie, N. O’Farrell, A. C. Barat, A. Marston, G. Coletta, P. L. Byrne, A. T. Prehn, J. H. Sci Rep Article Bevacizumab (bvz) is a first choice anti-angiogenic drug in oncology and is primarily administered in combination with chemotherapy. It has been hypothesized that anti-angiogenic drugs enhance efficacy of cytotoxic drugs by “normalizing” abnormal tumor vessels and improving drug penetration. Nevertheless, the clinical relevance of this phenomenon is still unclear with several studies over recent years suggesting an opposing relationship. Herein, we sought to develop a new computational tool to interrogate anti-angiogenic drug scheduling with particular application in the setting of colorectal cancer (CRC). Specifically, we have employed a mathematical model of vascular tumour growth which interrogates the impact of anti-angiogenic treatment and chemotherapeutic treatment on tumour volume. Model predictions were validated using CRC xenografts which underwent treatment with a clinically relevant combinatorial anti-angiogenic regimen. Bayesian model selection revealed the most appropriate term for capturing the effect of treatments on the tumour size, and provided insights into a switch-like dependence of FOLFOX delivery on the tumour vasculature. Our experimental data and mathematical model suggest that delivering chemotherapy prior to bvz may be optimal in the colorectal cancer setting. Nature Publishing Group UK 2018-07-25 /pmc/articles/PMC6060139/ /pubmed/30046049 http://dx.doi.org/10.1038/s41598-018-29318-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Sturrock, M. Miller, I. S. Kang, G. Hannis Arba’ie, N. O’Farrell, A. C. Barat, A. Marston, G. Coletta, P. L. Byrne, A. T. Prehn, J. H. Anti-angiogenic drug scheduling optimisation with application to colorectal cancer |
title | Anti-angiogenic drug scheduling optimisation with application to colorectal cancer |
title_full | Anti-angiogenic drug scheduling optimisation with application to colorectal cancer |
title_fullStr | Anti-angiogenic drug scheduling optimisation with application to colorectal cancer |
title_full_unstemmed | Anti-angiogenic drug scheduling optimisation with application to colorectal cancer |
title_short | Anti-angiogenic drug scheduling optimisation with application to colorectal cancer |
title_sort | anti-angiogenic drug scheduling optimisation with application to colorectal cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060139/ https://www.ncbi.nlm.nih.gov/pubmed/30046049 http://dx.doi.org/10.1038/s41598-018-29318-5 |
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