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Histone Signatures Predict Therapeutic Efficacy in Breast Cancer
Objective: Regulatory abnormalities caused by chromatin modifications are being increasingly recognized as contributors to cancer. While many molecularly targeted drugs have the potential to revert these modifications, their precise mechanism of action in cellular reprogramming is not known. Methods...
Formato: | Online Artículo Texto |
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Lenguaje: | English |
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IEEE
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207876/ https://www.ncbi.nlm.nih.gov/pubmed/32412527 http://dx.doi.org/10.1109/OJEMB.2020.2967105 |
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collection | PubMed |
description | Objective: Regulatory abnormalities caused by chromatin modifications are being increasingly recognized as contributors to cancer. While many molecularly targeted drugs have the potential to revert these modifications, their precise mechanism of action in cellular reprogramming is not known. Methods: To address this, we introduce an integrated phosphoprotein-histone-drug network (iPhDNet) approach to generate “global chromatin fingerprints of histone signatures.” The method integrates proteomic/phosphoproteomic, transcriptomic and regulatory genomic data to provide a causal mechanistic network and histone signatures of drug response. Results: We demonstrate the utility of iPhDNet in identifying H3K27me3K36me3 histone mark as a key fingerprint of response, mediated by chromatin remodelers BRD4, NSD3, EZH2, and a proto-oncogene MYC when treated with CDK inhibitors. Conclusions: We construct a regulatory network of breast cancer response to treatment and show that histone H3K27me3K36me3 status changes, driven by the BRD4/MYC pathway, upon treatment with drugs are hallmarks of response to treatment. |
format | Online Article Text |
id | pubmed-7207876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | IEEE |
record_format | MEDLINE/PubMed |
spelling | pubmed-72078762020-05-12 Histone Signatures Predict Therapeutic Efficacy in Breast Cancer IEEE Open J Eng Med Biol Article Objective: Regulatory abnormalities caused by chromatin modifications are being increasingly recognized as contributors to cancer. While many molecularly targeted drugs have the potential to revert these modifications, their precise mechanism of action in cellular reprogramming is not known. Methods: To address this, we introduce an integrated phosphoprotein-histone-drug network (iPhDNet) approach to generate “global chromatin fingerprints of histone signatures.” The method integrates proteomic/phosphoproteomic, transcriptomic and regulatory genomic data to provide a causal mechanistic network and histone signatures of drug response. Results: We demonstrate the utility of iPhDNet in identifying H3K27me3K36me3 histone mark as a key fingerprint of response, mediated by chromatin remodelers BRD4, NSD3, EZH2, and a proto-oncogene MYC when treated with CDK inhibitors. Conclusions: We construct a regulatory network of breast cancer response to treatment and show that histone H3K27me3K36me3 status changes, driven by the BRD4/MYC pathway, upon treatment with drugs are hallmarks of response to treatment. IEEE 2020-01-17 /pmc/articles/PMC7207876/ /pubmed/32412527 http://dx.doi.org/10.1109/OJEMB.2020.2967105 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Histone Signatures Predict Therapeutic Efficacy in Breast Cancer |
title | Histone Signatures Predict Therapeutic Efficacy in Breast Cancer |
title_full | Histone Signatures Predict Therapeutic Efficacy in Breast Cancer |
title_fullStr | Histone Signatures Predict Therapeutic Efficacy in Breast Cancer |
title_full_unstemmed | Histone Signatures Predict Therapeutic Efficacy in Breast Cancer |
title_short | Histone Signatures Predict Therapeutic Efficacy in Breast Cancer |
title_sort | histone signatures predict therapeutic efficacy in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207876/ https://www.ncbi.nlm.nih.gov/pubmed/32412527 http://dx.doi.org/10.1109/OJEMB.2020.2967105 |
work_keys_str_mv | AT histonesignaturespredicttherapeuticefficacyinbreastcancer AT histonesignaturespredicttherapeuticefficacyinbreastcancer |