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In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer
The multistep development of cancer involves the cooperation between multiple molecular lesions, as well as complex interactions between cancer cells and the surrounding tumour microenvironment. The search for these synergistic interactions using experimental models made tremendous contributions to...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125147/ https://www.ncbi.nlm.nih.gov/pubmed/34063110 http://dx.doi.org/10.3390/ijms22094897 |
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author | Selvaggio, Gianluca Chaouiya, Claudine Janody, Florence |
author_facet | Selvaggio, Gianluca Chaouiya, Claudine Janody, Florence |
author_sort | Selvaggio, Gianluca |
collection | PubMed |
description | The multistep development of cancer involves the cooperation between multiple molecular lesions, as well as complex interactions between cancer cells and the surrounding tumour microenvironment. The search for these synergistic interactions using experimental models made tremendous contributions to our understanding of oncogenesis. Yet, these approaches remain labour-intensive and challenging. To tackle such a hurdle, an integrative, multidisciplinary effort is required. In this article, we highlight the use of logical computational models, combined with experimental validations, as an effective approach to identify cooperative mechanisms and therapeutic strategies in the context of cancer biology. In silico models overcome limitations of reductionist approaches by capturing tumour complexity and by generating powerful testable hypotheses. We review representative examples of logical models reported in the literature and their validation. We then provide further analyses of our logical model of Epithelium to Mesenchymal Transition (EMT), searching for additional cooperative interactions involving inputs from the tumour microenvironment and gain of function mutations in NOTCH. |
format | Online Article Text |
id | pubmed-8125147 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81251472021-05-17 In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer Selvaggio, Gianluca Chaouiya, Claudine Janody, Florence Int J Mol Sci Review The multistep development of cancer involves the cooperation between multiple molecular lesions, as well as complex interactions between cancer cells and the surrounding tumour microenvironment. The search for these synergistic interactions using experimental models made tremendous contributions to our understanding of oncogenesis. Yet, these approaches remain labour-intensive and challenging. To tackle such a hurdle, an integrative, multidisciplinary effort is required. In this article, we highlight the use of logical computational models, combined with experimental validations, as an effective approach to identify cooperative mechanisms and therapeutic strategies in the context of cancer biology. In silico models overcome limitations of reductionist approaches by capturing tumour complexity and by generating powerful testable hypotheses. We review representative examples of logical models reported in the literature and their validation. We then provide further analyses of our logical model of Epithelium to Mesenchymal Transition (EMT), searching for additional cooperative interactions involving inputs from the tumour microenvironment and gain of function mutations in NOTCH. MDPI 2021-05-05 /pmc/articles/PMC8125147/ /pubmed/34063110 http://dx.doi.org/10.3390/ijms22094897 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Selvaggio, Gianluca Chaouiya, Claudine Janody, Florence In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer |
title | In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer |
title_full | In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer |
title_fullStr | In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer |
title_full_unstemmed | In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer |
title_short | In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer |
title_sort | in silico logical modelling to uncover cooperative interactions in cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125147/ https://www.ncbi.nlm.nih.gov/pubmed/34063110 http://dx.doi.org/10.3390/ijms22094897 |
work_keys_str_mv | AT selvaggiogianluca insilicologicalmodellingtouncovercooperativeinteractionsincancer AT chaouiyaclaudine insilicologicalmodellingtouncovercooperativeinteractionsincancer AT janodyflorence insilicologicalmodellingtouncovercooperativeinteractionsincancer |