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Biological signalling networks model how signals are transmitted and how activities are coordinated in the cell. The study of the structure of such networks in complex diseases such as cancer can provide insights into how they function, and consequently, suggest suitable treatment approaches. Here, we explored such topological characteristics in the example of a mitogen-activated protein kinase (MAPK) signalling network derived from published studies in cancer. We employed well-established techniques to conduct network analyses, and collected information on gene function as obtained from large-scale public databases. This allowed us to map topological and functional relationships, and build hypotheses on this network\u2019s functional consequences. In particular, we find that the topology of this MAPK network is highly non-random, modular and robust. Moreover, analysis of the network\u2019s structure indicates the presence of organisational features of cancer hallmarks, expressed in an asymmetrical manner across communities of the network. Finally, our results indicate that the organisation of this network renders it problematic to use treatment approaches that focus on a single target. Our analysis suggests that multi-target attacks in a well-orchestrated manner are required to alter how the network functions. Overall, we propose that complex network analyses combined with pharmacological insights will help inform on future treatment strategies, exploiting structural vulnerabilities of signalling and regulatory networks in cancer.<\/jats:p>","DOI":"10.3390\/sym14051009","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T21:36:06Z","timestamp":1652736966000},"page":"1009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Structural Characterisation of the Mitogen-Activated Protein Kinase Network in Cancer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6815-985X","authenticated-orcid":false,"given":"Evangelos","family":"Chatzaroulas","sequence":"first","affiliation":[{"name":"School of Computer Science and Electronic Engineering, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vytenis","family":"Sliogeris","sequence":"additional","affiliation":[{"name":"School of Computer Science and Electronic Engineering, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Victori","sequence":"additional","affiliation":[{"name":"Computational Biology and Integrative Genomics Lab, Department of Oncology, Medical Sciences Division, University of Oxford, Oxford OX3 7DQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca M.","family":"Buffa","sequence":"additional","affiliation":[{"name":"Computational Biology and Integrative Genomics Lab, Department of Oncology, Medical Sciences Division, University of Oxford, Oxford OX3 7DQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0164-8322","authenticated-orcid":false,"given":"Sotiris","family":"Moschoyiannis","sequence":"additional","affiliation":[{"name":"School of Computer Science and Electronic Engineering, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7268-9359","authenticated-orcid":false,"given":"Roman","family":"Bauer","sequence":"additional","affiliation":[{"name":"School of Computer Science and Electronic Engineering, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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