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Precision medicine driven by cancer systems biology
Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated pr...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385204/ https://www.ncbi.nlm.nih.gov/pubmed/28265786 http://dx.doi.org/10.1007/s10555-017-9662-4 |
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author | Filipp, Fabian V. |
author_facet | Filipp, Fabian V. |
author_sort | Filipp, Fabian V. |
collection | PubMed |
description | Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors. Mutation hotspots, structural modeling, UV signature, and genomic as well as non-genomic mechanisms of disease initiation and progression are taken into consideration to identify resistance mutations and novel drug targets. A comprehensive precision medicine profile of a malignant melanoma patient illustrates future rational drug targeting strategies. Network analysis emphasizes an important role of epigenetic and metabolic master regulators in oncogenesis. Co-occurrence of driver mutations in signaling, metabolic, and epigenetic factors highlights how cumulative alterations of our genomes and epigenomes progressively lead to uncontrolled cell proliferation. Precision insights have the ability to identify independent molecular pathways suitable for drug targeting. Synergistic treatment combinations of orthogonal modalities including immunotherapy, mitogen-activated protein kinase inhibitors, epigenetic inhibitors, and metabolic inhibitors have the potential to overcome immune evasion, side effects, and drug resistance. |
format | Online Article Text |
id | pubmed-5385204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-53852042017-04-24 Precision medicine driven by cancer systems biology Filipp, Fabian V. Cancer Metastasis Rev Article Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors. Mutation hotspots, structural modeling, UV signature, and genomic as well as non-genomic mechanisms of disease initiation and progression are taken into consideration to identify resistance mutations and novel drug targets. A comprehensive precision medicine profile of a malignant melanoma patient illustrates future rational drug targeting strategies. Network analysis emphasizes an important role of epigenetic and metabolic master regulators in oncogenesis. Co-occurrence of driver mutations in signaling, metabolic, and epigenetic factors highlights how cumulative alterations of our genomes and epigenomes progressively lead to uncontrolled cell proliferation. Precision insights have the ability to identify independent molecular pathways suitable for drug targeting. Synergistic treatment combinations of orthogonal modalities including immunotherapy, mitogen-activated protein kinase inhibitors, epigenetic inhibitors, and metabolic inhibitors have the potential to overcome immune evasion, side effects, and drug resistance. Springer US 2017-03-07 2017 /pmc/articles/PMC5385204/ /pubmed/28265786 http://dx.doi.org/10.1007/s10555-017-9662-4 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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. |
spellingShingle | Article Filipp, Fabian V. Precision medicine driven by cancer systems biology |
title | Precision medicine driven by cancer systems biology |
title_full | Precision medicine driven by cancer systems biology |
title_fullStr | Precision medicine driven by cancer systems biology |
title_full_unstemmed | Precision medicine driven by cancer systems biology |
title_short | Precision medicine driven by cancer systems biology |
title_sort | precision medicine driven by cancer systems biology |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385204/ https://www.ncbi.nlm.nih.gov/pubmed/28265786 http://dx.doi.org/10.1007/s10555-017-9662-4 |
work_keys_str_mv | AT filippfabianv precisionmedicinedrivenbycancersystemsbiology |