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Title: Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

Abstract

We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

Authors:
 [1];  [2]; ; ;  [3];  [4];  [4]; ;  [5];  [4]
  1. Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS, Cachan 94230 Cedex, France & INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France)
  2. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW 2052 (Australia)
  3. Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France)
  4. (France)
  5. Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris (France)
Publication Date:
OSTI Identifier:
22608982
Resource Type:
Journal Article
Journal Name:
AIP Conference Proceedings
Additional Journal Information:
Journal Volume: 1738; Journal Issue: 1; Conference: ICNAAM 2015: International conference of numerical analysis and applied mathematics 2015, Rhodes (Greece), 22-28 Sep 2015; Other Information: (c) 2016 Author(s); Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0094-243X
Country of Publication:
United States
Language:
English
Subject:
71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSICS; BIOLOGY; BIOPHYSICS; DRUGS; EVOLUTION; LAWS; NEOPLASMS; POPULATIONS; POTENTIALS; PROLIFERATION; SIMULATION

Citation Formats

Lorenzi, Tommaso, Chisholm, Rebecca H., Lorz, Alexander, Neves de Almeida, Luís, Clairambault, Jean, CNRS, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris, INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex, Larsen, Annette K., Escargueil, Alexandre, and INSERM, UMR-S 938, Laboratory of “Cancer Biology and Therapeutics”, F-75012, Paris. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences. United States: N. p., 2016. Web. doi:10.1063/1.4952112.
Lorenzi, Tommaso, Chisholm, Rebecca H., Lorz, Alexander, Neves de Almeida, Luís, Clairambault, Jean, CNRS, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris, INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex, Larsen, Annette K., Escargueil, Alexandre, & INSERM, UMR-S 938, Laboratory of “Cancer Biology and Therapeutics”, F-75012, Paris. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences. United States. doi:10.1063/1.4952112.
Lorenzi, Tommaso, Chisholm, Rebecca H., Lorz, Alexander, Neves de Almeida, Luís, Clairambault, Jean, CNRS, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris, INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex, Larsen, Annette K., Escargueil, Alexandre, and INSERM, UMR-S 938, Laboratory of “Cancer Biology and Therapeutics”, F-75012, Paris. Wed . "Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences". United States. doi:10.1063/1.4952112.
@article{osti_22608982,
title = {Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences},
author = {Lorenzi, Tommaso and Chisholm, Rebecca H. and Lorz, Alexander and Neves de Almeida, Luís and Clairambault, Jean and CNRS, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris and INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex and Larsen, Annette K. and Escargueil, Alexandre and INSERM, UMR-S 938, Laboratory of “Cancer Biology and Therapeutics”, F-75012, Paris},
abstractNote = {We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.},
doi = {10.1063/1.4952112},
journal = {AIP Conference Proceedings},
issn = {0094-243X},
number = 1,
volume = 1738,
place = {United States},
year = {2016},
month = {6}
}