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H 1 Non-genetic cancer cell plasticity

Auteurs : Pisco, Angela (Auteur de la Conférence)
CIRM (Editeur )

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    Résumé : Therapy resistance and tumour relapse after drug therapy are commonly explained by Darwinian selection of pre-existing drug-resistant, often stem-like cancer cells resulting from random mutations. However, the ubiquitous nongenetic heterogeneity and plasticity of tumour cell phenotype raises the question: are mutations really necessary and sufficient to promote cell phenotype changes during tumour progression? Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. Cancer therapy inevitably spares some cancer cells, even in the absence of resistant mutants. Accumulating observations suggest that the non-killed, residual tumour cells actively acquire a new phenotype simply by exploiting their developmental potential. These surviving cells are stressed by the cytotoxic treatment, and owing to phenotype plasticity, exhibit a variety of responses. By entering such stem-like, stress-response states, the surviving cells strengthen their capacity to cope with future noxious agents. Considering nongenetic cell state dynamics and the relative ease with which surviving but stressed cells can be tipped into latent attractors of the gene regulatory network provides a foundation for exploring new therapeutic approaches that seek not only to kill cancer cells but also to avoid promoting resistance and relapse that are inherently linked to the attempts to kill them.

    Keywords: cancer attractor, epigenetic landscape, multi-drug resistance

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

      Informations sur la Vidéo

      Langue : Anglais
      Date de publication : 19/01/16
      Date de captation : 10/12/15
      Collection : Research talks ; Mathematics in Science and Technology
      Format : MP4
      Durée : 00:33:58
      Domaine : Mathematics in Science & Technology
      Audience : Chercheurs ; Doctorants , Post - Doctorants
      Download : https://videos.cirm-math.fr/2015-12-10_Pisco.mp4

    Informations sur la rencontre

    Nom de la rencontre : Present challenges of mathematics in oncology and biology of cancer / Nouveaux défis des mathématiques en oncologie et biologie du cancer
    Organisateurs de la rencontre : André, Nicolas ; Barbolosi, Dominique ; Benabdallah, Assia ; Hubert, Florence
    Dates : 07/12/15 - 11/12/15
    Année de la rencontre : 2015
    URL Congrès : http://conferences.cirm-math.fr/1412.html

    Citation Data

    DOI : 10.24350/CIRM.V.18908503
    Cite this video as: Pisco, Angela (2015). Non-genetic cancer cell plasticity. CIRM. Audiovisual resource. doi:10.24350/CIRM.V.18908503
    URI : http://dx.doi.org/10.24350/CIRM.V.18908503


    1. Pisco, A. O., & Huang, S. (2015). Non-genetic cancer cell plasticity and therapy-induced stemness in tumour relapse: ‘What does not kill me strengthens me’. British Journal of Cancer, 112, 1725–1732 - http://dx.doi.org/10.1038/bjc.2015.146

    2. Pisco, A. O., Jackson, D. A., & Huang, S. (2014). Reduced Intracellular Drug Accumulation in Drug-Resistant Leukemia Cells is Not Only Solely Due to MDR-Mediated Efflux but also to Decreased Uptake. Frontiers in Oncology, 4, 306 - http://doi.org/10.3389/fonc.2014.00306

    3. Pisco, A. O., Brock, A., Zhou, J., Moor, A., Mojtahedi, M., Jackson D., & Huang, S. (2013). Non-Darwinian dynamics in therapy-induced cancer drug resistance. Nature Communications, 4, 2467 - http://dx.doi.org/10.1038/ncomms3467

    4. Zhou, J., Pisco, A. O., Qian, H., & Huang, S. (2014). Nonequilibrium Population Dynamics of Phenotype Conversion of Cancer Cells. PLoS ONE, 9(12), 110714 - http://dx.doi.org/10.1371/journal.pone.0110714

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