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A mathematical theory of the transcription repression (TR) therapy of cancer – whether and how it may work
Transcription repression (TR) therapy of cancer has been widely discussed. Here, TR refers to global repression of transcription rather than specific targeting of cancer-causing genes such as MYC. TR drugs inhibit transcription by binding to the transcribed DNA or to RNA polymerase; for example, act...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503560/ https://www.ncbi.nlm.nih.gov/pubmed/28454100 http://dx.doi.org/10.18632/oncotarget.16957 |
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author | Chen, Yuxin Wen, Haijun Wu, Chung-I |
author_facet | Chen, Yuxin Wen, Haijun Wu, Chung-I |
author_sort | Chen, Yuxin |
collection | PubMed |
description | Transcription repression (TR) therapy of cancer has been widely discussed. Here, TR refers to global repression of transcription rather than specific targeting of cancer-causing genes such as MYC. TR drugs inhibit transcription by binding to the transcribed DNA or to RNA polymerase; for example, actinomycin D has been extensively used in research and therapy to shut down transcription globally [1–7]. As proliferating cells demand a high rate of transcription, restricting transcript production could be effective in slowing down cell proliferation. However, TR also deprives other less proliferative cells of new transcripts, thus leading to substantial toxicity [1, 8, 9]. We now develop a mathematical theory to exploit the greater demand for transcription in highly proliferating cells. A new strategy, referred to as the TRR (transcript repression-recovery) model, would insert a recovery phase to allow the more slowly proliferating cells to recover. It is most effective to have strong blocking for a short period (a few hours) followed by a longer recovery phase in each cell cycle. Hence, TRR can potentially achieve selective killing of cells based on their global transcription needs but precise fine-tuning is necessary. |
format | Online Article Text |
id | pubmed-5503560 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-55035602017-07-11 A mathematical theory of the transcription repression (TR) therapy of cancer – whether and how it may work Chen, Yuxin Wen, Haijun Wu, Chung-I Oncotarget Research Paper Transcription repression (TR) therapy of cancer has been widely discussed. Here, TR refers to global repression of transcription rather than specific targeting of cancer-causing genes such as MYC. TR drugs inhibit transcription by binding to the transcribed DNA or to RNA polymerase; for example, actinomycin D has been extensively used in research and therapy to shut down transcription globally [1–7]. As proliferating cells demand a high rate of transcription, restricting transcript production could be effective in slowing down cell proliferation. However, TR also deprives other less proliferative cells of new transcripts, thus leading to substantial toxicity [1, 8, 9]. We now develop a mathematical theory to exploit the greater demand for transcription in highly proliferating cells. A new strategy, referred to as the TRR (transcript repression-recovery) model, would insert a recovery phase to allow the more slowly proliferating cells to recover. It is most effective to have strong blocking for a short period (a few hours) followed by a longer recovery phase in each cell cycle. Hence, TRR can potentially achieve selective killing of cells based on their global transcription needs but precise fine-tuning is necessary. Impact Journals LLC 2017-04-08 /pmc/articles/PMC5503560/ /pubmed/28454100 http://dx.doi.org/10.18632/oncotarget.16957 Text en Copyright: © 2017 Chen et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Chen, Yuxin Wen, Haijun Wu, Chung-I A mathematical theory of the transcription repression (TR) therapy of cancer – whether and how it may work |
title | A mathematical theory of the transcription repression (TR) therapy of cancer – whether and how it may work |
title_full | A mathematical theory of the transcription repression (TR) therapy of cancer – whether and how it may work |
title_fullStr | A mathematical theory of the transcription repression (TR) therapy of cancer – whether and how it may work |
title_full_unstemmed | A mathematical theory of the transcription repression (TR) therapy of cancer – whether and how it may work |
title_short | A mathematical theory of the transcription repression (TR) therapy of cancer – whether and how it may work |
title_sort | mathematical theory of the transcription repression (tr) therapy of cancer – whether and how it may work |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503560/ https://www.ncbi.nlm.nih.gov/pubmed/28454100 http://dx.doi.org/10.18632/oncotarget.16957 |
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