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Global Dormancy of Metastases due to Systemic Inhibition of Angiogenesis

hal.structure.identifierModélisation, contrôle et calcul [MC2]
hal.structure.identifierCenter of Cancer and Systems Biology [CCSB]
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
dc.contributor.authorBENZEKRY, Sébastien
hal.structure.identifierIstituto di Analisi dei Sistemi ed Informatica "A. Ruberti"
dc.contributor.authorGANDOLFI, Alberto
hal.structure.identifierCenter of Cancer and Systems Biology [CCSB]
dc.contributor.authorHAHNFELDT, Philip
dc.date.issued2014-01-21
dc.identifier.issn1932-6203
dc.description.abstractEnAutopsy studies of adults dying of non-cancer causes have shown that virtually all of us possess occult, cancerous lesions. This suggests that, for most individuals, cancer will become dormant and not progress, while only in some will it become symptomatic disease. Meanwhile, it was recently shown in animal models that a tumor can produce both stimulators and inhibitors of its own blood supply. To explain the autopsy findings in light of the preclinical research data, we propose a mathematical model of cancer development at the organism scale describing a growing population of metastases, which, together with the primary tumor, can exert a progressively greater level of systemic angiogenesis-inhibitory influence that eventually overcomes local angiogenesis stimulation to suppress the growth of all lesions. We integrate over this increasingly negative global signaling from all sources to track the development of total tumor burden. This in silico study of the dynamics of the tumor/metastasis system identifies ranges of parameter values where mutual angio-inhibitory interactions within a population of tumor lesions could yield global dormancy, i.e., an organism-level homeostatic steady state in total tumor burden. Given that mortality arises most often from metastases rather than growth of the primary, this finding may have important therapeutic implications
dc.language.isoen
dc.publisherPublic Library of Science
dc.subject.enMetastasis
dc.subject.enDormancy
dc.subject.enAngiogenesis inhibition
dc.subject.enMathematical model
dc.title.enGlobal Dormancy of Metastases due to Systemic Inhibition of Angiogenesis
dc.typeArticle de revue
dc.identifier.doi10.1371/journal.pone.0084249
dc.subject.halSciences du Vivant [q-bio]/Cancer
bordeaux.journalPLoS ONE
bordeaux.pagee84249
bordeaux.volume9
bordeaux.issue1
bordeaux.peerReviewedoui
hal.identifierhal-00868592
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-00868592v1
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