Phenotype heterogeneity in cancer cell populations

Abstract : Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to represent evolution towards heterogeneity, possibly polyclonal, in cancer cell populations and propose innovative directions for therapeutic strategies based on such frameworks.
Type de document :
Communication dans un congrès
ICNAAM 2015 Session 70: "Mathematical models and methods to investigate heterogeneity in cell and cell population biology'', Sep 2015, Rhodes, Greece. AIP Proceedings of ICNAAM 2015, 〈http://history.icnaam.org/icnaam_2015/index.html〉
Liste complète des métadonnées

Littérature citée [13 références]  Voir  Masquer  Télécharger

https://hal.inria.fr/hal-01249242
Contributeur : Jean Clairambault <>
Soumis le : mercredi 30 décembre 2015 - 19:14:03
Dernière modification le : jeudi 11 janvier 2018 - 06:27:34
Document(s) archivé(s) le : mardi 5 avril 2016 - 13:50:20

Fichier

JC_ICNAAM2015Rhodes.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

  • HAL Id : hal-01249242, version 1

Collections

Citation

Luis Almeida, Rebecca H. Chisholm, Jean Clairambault, Alexandre Escargueil, Tommaso Lorenzi, et al.. Phenotype heterogeneity in cancer cell populations. ICNAAM 2015 Session 70: "Mathematical models and methods to investigate heterogeneity in cell and cell population biology'', Sep 2015, Rhodes, Greece. AIP Proceedings of ICNAAM 2015, 〈http://history.icnaam.org/icnaam_2015/index.html〉. 〈hal-01249242〉

Partager

Métriques

Consultations de la notice

360

Téléchargements de fichiers

80