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Mathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth

hal.structure.identifierModélisation Mathématique pour l'Oncologie [MONC]
dc.contributor.authorBENZEKRY, Sébastien
hal.structure.identifierCenter of Cancer and Systems Biology [CCSB]
dc.contributor.authorLAMONT, Clare
hal.structure.identifierSimulation & Modelling : Adaptive Response for Therapeutics in Cancer [SMARTc unit]
dc.contributor.authorBARBOLOSI, Dominique
hal.structure.identifierCenter of Cancer and Systems Biology [CCSB]
dc.contributor.authorHLATKY, Lynn
hal.structure.identifierCenter of Cancer and Systems Biology [CCSB]
dc.contributor.authorHAHNFELDT, Philip
dc.date.accessioned2024-04-04T03:09:37Z
dc.date.available2024-04-04T03:09:37Z
dc.date.issued2017
dc.identifier.issn0008-5472
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/193622
dc.description.abstractEnInteractions between different tumors within the same organism have major clinical implications, especially in the context of surgery and metastatic disease. Three main explanatory theories (competition, angiogenesis inhibition and proliferation inhibition) have been proposed but precise determinants of the phenomenon remain poorly understood. Here we formalized these theories into mathematical models and performed biological experiments to test them with empirical data. In syngeneic mice bearing two simultaneously implanted tumors, growth of only one of the tumors was significantly suppressed (61% size reduction at day 15, p<0.05). The competition model had to be rejected while the angiogenesis inhibition and proliferation inhibition models were able to describe the data. Additional models including a theory based on distant cytotoxic log-kill effects were unable to fit the data. The proliferation inhibition model was identifiable and minimal (4 parameters), and its descriptive power was validated against the data, including consistency in predictions of single tumor growth when no secondary tumor was present. This theory may also shed new light on single cancer growth insofar as it offers a biologically translatable picture of how local and global action may combine to control local tumor growth, and in particular, the role of tumor-tumor inhibition. This model offers a depiction of concomitant resistance that provides an improved theoretical basis for tumor growth control and may also find utility in therapeutic planning to avoid post-surgery metastatic acceleration.Major findingsIn mice bearing two tumors implanted simultaneously, tumor growth was suppressed in one of the two tumors. Three theories of this phenomenon were advanced and assessed against the data. As formalized, a model of competition for nutrients was not able to explain the growth behavior as well as indirect, angiogenesis-regulated inhibition or a third model based on direct systemic inhibition. This last model offers a depiction of concomitant resistance that provides an improved theoretical basis for tumor growth control and may also find utility in therapeutic planning to avoid post- surgery metastatic acceleration.
dc.language.isoen
dc.publisherAmerican Association for Cancer Research
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/
dc.subject.meshNeoplasms
dc.subject.meshCarcinoma, Lewis Lung
dc.subject.meshAngiogenesis Inhibitors
dc.title.enMathematical modeling of tumor-tumor distant interactions supports a systemic control of tumor growth
dc.typeArticle de revue
dc.identifier.doi10.1158/0008-5472.CAN-17-0564
dc.subject.halSciences du Vivant [q-bio]/Cancer
bordeaux.journalCancer Research
bordeaux.hal.laboratoriesInstitut de Mathématiques de Bordeaux (IMB) - UMR 5251*
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-01566947
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-01566947v1
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Cancer%20Research&amp;rft.date=2017&amp;rft.eissn=0008-5472&amp;rft.issn=0008-5472&amp;rft.au=BENZEKRY,%20S%C3%A9bastien&amp;LAMONT,%20Clare&amp;BARBOLOSI,%20Dominique&amp;HLATKY,%20Lynn&amp;HAHNFELDT,%20Philip&amp;rft.genre=article


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