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H 1 Modeling the chemotherapy-induced selection of drug-resistant traits during tumor growth

Auteurs : Levy, Doron (Auteur de la Conférence)
CIRM (Editeur )

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    Résumé : The emergence of drug-resistance is a major challenge in chemotherapy. In this talk we will present our recent mathematical models for describing the dynamics of drug-resistance in solid tumors. Our models follow the dynamics of the tumor, assuming that the cancer cell population depends on a phenotype variable that corresponds to the resistance level to a cytotoxic drug. We incorporate the dynamics of nutrients and two different types of drugs: a cytotoxic drug, which directly impacts the death rate of the cancer cells, and a cytostatic drug that reduces the proliferation rate. Through analysis and simulations, we study the impact of spatial and phenotypic heterogeneity on the tumor growth under chemotherapy. We demonstrate that heterogeneous cancer cells may emerge due to the selection dynamics of the environment. Our models predict that under certain conditions, multiple resistant traits emerge at different locations within the tumor. We show that a higher dosage of the cytotoxic drug may delay a relapse, yet, when this happens, a more resistant trait emerges. Moreover, we estimate the expansion rate of the tumor boundary as well as the time of relapse, in terms of the resistance trait, the level of the nutrient, and the drug concentration. Finally, we propose an efficient drug schedule aiming at minimizing the growth rate of the most resistant trait. By combining the cytotoxic and cytostatic drugs, we demonstrate that the resistant cells can be eliminated.

    Keywords : tumor growth; drug-resistance; cancer dynamics; chemotherapy; heterogeneity

    Codes MSC :
    92C37 - Cell biology
    92C40 - Biochemistry, molecular biology
    92C50 - Medical applications of mathematical biology

      Informations sur la Vidéo

      Réalisateur : Hennenfent, Guillaume
      Langue : Anglais
      Date de publication : 12/07/2018
      Date de captation : 10/07/2018
      Collection : Research talks
      Format : MP4
      Durée : 01:03:48
      Domaine : Mathematics in Science & Technology ; PDE ; Numerical Analysis & Scientific Computing
      Audience : Chercheurs ; Doctorants , Post - Doctorants
      Download : https://videos.cirm-math.fr/2018-07-10_Levy.mp4

    Informations sur la rencontre

    Nom de la rencontre : Mathematical perspectives in the biology and therapeutics of cancer​ / Perspectives mathématiques en biologie et thérapie du cancer
    Organisateurs de la rencontre : Chapuisat, Guillemette ; Clairambault, Jean ; Hubert, Florence ; Ledzewicz, Urszula ; Volpert, Vitaly
    Dates : 09/07/2018 - 13/07/2018
    Année de la rencontre : 2018
    URL Congrès : https://conferences.cirm-math.fr/1752.html

    Citation Data

    DOI : 10.24350/CIRM.V.19419903
    Cite this video as: Levy, Doron (2018). Modeling the chemotherapy-induced selection of drug-resistant traits during tumor growth. CIRM. Audiovisual resource. doi:10.24350/CIRM.V.19419903
    URI : http://dx.doi.org/10.24350/CIRM.V.19419903


    Voir aussi

    Bibliographie

    1. Becker, M., & Levy, D. (2017). Modeling the transfer of drug resistance in solid tumors. Bulletin of Mathematical Biology, 79(10), 2394–2412 - https://doi.org/10.1007/s11538-017-0334-x

    2. Cho, H., & Levy, D. (2018). Modeling the chemotherapy-induced selection of drug-resistant traits during tumor growth. Journal of Theoretical Biology, 436, 120-134 - https://doi.org/10.1016/j.jtbi.2017.10.005

    3. Cho, H., & Levy, D. (2017). Modeling the dynamics of heterogeneity of solid tumors in response to chemotherapy. Bulletin of Mathematical Biology, 79(12), 2986-3012 - https://doi.org/10.1007/s11538-017-0359-1

    4. Greene, J., Lavi, O., Gottesman, M., & Levy, D. (2014). The impact of cell density and mutations in a model of multidrug resistance in solid tumors. Bulletin of Mathematical Biology, 76(3), 627–653 - https://doi.org/10.1007/s11538-014-9936-8

    5. Tomasetti, C., & Levy, D. (2010). An elementary approach to modeling drug resistance in cancer. Mathematical Biosciences and Engineering, 7(4), 905-918 - https://doi.org/10.3934/mbe.2010.7.905

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