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Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks

Organ toxicity in cancer therapy is likely caused by an underlying disposition for given pathophysiological mechanisms in the individual patient. Mechanistic data on treatment toxicity at the patient level are scarce; hence, probabilistic and translational linkages among different layers of data inf...

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Autores principales: Ree, Anne Hansen, Meltzer, Sebastian, Flatmark, Kjersti, Dueland, Svein, Kalanxhi, Erta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284741/
https://www.ncbi.nlm.nih.gov/pubmed/25501337
http://dx.doi.org/10.3390/ijms151222835
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author Ree, Anne Hansen
Meltzer, Sebastian
Flatmark, Kjersti
Dueland, Svein
Kalanxhi, Erta
author_facet Ree, Anne Hansen
Meltzer, Sebastian
Flatmark, Kjersti
Dueland, Svein
Kalanxhi, Erta
author_sort Ree, Anne Hansen
collection PubMed
description Organ toxicity in cancer therapy is likely caused by an underlying disposition for given pathophysiological mechanisms in the individual patient. Mechanistic data on treatment toxicity at the patient level are scarce; hence, probabilistic and translational linkages among different layers of data information, all the way from cellular targets of the therapeutic exposure to tissues and ultimately the patient’s organ systems, are required. Throughout all of these layers, untoward treatment effects may be viewed as perturbations that propagate within a hierarchically structured network from one functional level to the next, at each level causing disturbances that reach a critical threshold, which ultimately are manifested as clinical adverse reactions. Advances in bioinformatics permit compilation of information across the various levels of data organization, presumably enabling integrated systems biology-based prediction of treatment safety. In view of the complexity of biological responses to cancer therapy, this communication reports on a “top-down” strategy, starting with the systematic assessment of adverse effects within a defined therapeutic context and proceeding to transcriptomic and proteomic analysis of relevant patient tissue samples and computational exploration of the resulting data, with the ultimate aim of utilizing information from functional connectivity networks in evaluation of patient safety in multimodal cancer therapy.
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spelling pubmed-42847412015-01-21 Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks Ree, Anne Hansen Meltzer, Sebastian Flatmark, Kjersti Dueland, Svein Kalanxhi, Erta Int J Mol Sci Review Organ toxicity in cancer therapy is likely caused by an underlying disposition for given pathophysiological mechanisms in the individual patient. Mechanistic data on treatment toxicity at the patient level are scarce; hence, probabilistic and translational linkages among different layers of data information, all the way from cellular targets of the therapeutic exposure to tissues and ultimately the patient’s organ systems, are required. Throughout all of these layers, untoward treatment effects may be viewed as perturbations that propagate within a hierarchically structured network from one functional level to the next, at each level causing disturbances that reach a critical threshold, which ultimately are manifested as clinical adverse reactions. Advances in bioinformatics permit compilation of information across the various levels of data organization, presumably enabling integrated systems biology-based prediction of treatment safety. In view of the complexity of biological responses to cancer therapy, this communication reports on a “top-down” strategy, starting with the systematic assessment of adverse effects within a defined therapeutic context and proceeding to transcriptomic and proteomic analysis of relevant patient tissue samples and computational exploration of the resulting data, with the ultimate aim of utilizing information from functional connectivity networks in evaluation of patient safety in multimodal cancer therapy. MDPI 2014-12-09 /pmc/articles/PMC4284741/ /pubmed/25501337 http://dx.doi.org/10.3390/ijms151222835 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ree, Anne Hansen
Meltzer, Sebastian
Flatmark, Kjersti
Dueland, Svein
Kalanxhi, Erta
Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks
title Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks
title_full Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks
title_fullStr Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks
title_full_unstemmed Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks
title_short Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks
title_sort biomarkers of treatment toxicity in combined-modality cancer therapies with radiation and systemic drugs: study design, multiplex methods, molecular networks
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284741/
https://www.ncbi.nlm.nih.gov/pubmed/25501337
http://dx.doi.org/10.3390/ijms151222835
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