Modelling the effects of cell-cycle heterogeneity on the response of a solid tumour to chemotherapy: biological insights from a hybrid multiscale cellular automaton model

Journal of Theoretical Biology
Gibin G PowathilMark A J Chaplain


The therapeutic control of a solid tumour depends critically on the responses of the individual cells that constitute the entire tumour mass. A particular cell's spatial location within the tumour and intracellular interactions, including the evolution of the cell-cycle within each cell, has an impact on their decision to grow and divide. They are also influenced by external signals from other cells as well as oxygen and nutrient concentrations. Hence, it is important to take these into account when modelling tumour growth and the response to various treatment regimes ('cell-kill therapies'), including chemotherapy. In order to address this multiscale nature of solid tumour growth and its response to treatment, we propose a hybrid, individual-based approach that analyses spatio-temporal dynamics at the level of cells, linking individual cell behaviour with the macroscopic behaviour of cell organisation and the microenvironment. The individual tumour cells are modelled by using a cellular automaton (CA) approach, where each cell has its own internal cell-cycle, modelled using a system of ODEs. The internal cell-cycle dynamics determine the growth strategy in the CA model, making it more predictive and biologically relevant. It a...Continue Reading


Sep 26, 2013·Acta Biotheoretica·Samuel Bernard
Apr 2, 2013·Clinical & Experimental Metastasis·Maymona Al-Husari, Steven D Webb
Dec 19, 2013·Mathematical Biosciences·B Bedessem, A Stéphanou
Aug 29, 2013·Journal of Mathematical Biology·Maymona Al-HusariSteven D Webb
Feb 28, 2013·Expert Opinion on Drug Delivery·Abraham H Abouzeid, Vladimir P Torchilin
Sep 15, 2014·Journal of Theoretical Biology·R Penta, D Ambrosi
Jun 16, 2015·Journal of Theoretical Biology·M SturrockGrzegorz A Rempala
May 6, 2014·Seminars in Cancer Biology·Zhihui WangThomas S Deisboeck
Jun 8, 2015·Advances in Anatomic Pathology·Mark C LloydMarilyn M Bui
Oct 28, 2014·Applied Mathematics·Jan Poleszczuk, Heiko Enderling
Apr 3, 2015·Journal of the Royal Society, Interface·Aurelio A de Los Reyes VYangjin Kim
Mar 13, 2014·Journal of Theoretical Biology·Munju KimKatarzyna A Rejniak
Jul 17, 2012·Journal of Theoretical Biology·Pierre GabrielGlenn F Webb
Mar 13, 2014·Seminars in Cancer Biology·Gibin G PowathilMark A J Chaplain
Jan 16, 2015·Journal of Pharmacokinetics and Pharmacodynamics·Zhihui WangThomas S Deisboeck
Jul 31, 2012·PloS One·Hugues BersiniVéronique Thomas-Vaslin
Feb 7, 2017·PloS One·Wanho LeeYangjin Kim
Aug 15, 2015·PloS One·Harald KempfMichael Meyer-Hermann
Aug 29, 2017·PloS One·Mohammad Hossein Zangooei, Jafar Habibi
Feb 12, 2019·JCO Clinical Cancer Informatics·Sara HamisMark A J Chaplain
Apr 29, 2020·Nature Reviews. Cancer·Matthew A Clarke, Jasmin Fisher
Mar 24, 2018·International Journal of Oncology·Zhanhui DuShangming Liu
Jul 25, 2019·Bulletin of Mathematical Biology·Renee Brady, Heiko Enderling
Jul 28, 2020·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Yangjin KimSean Lawler
Oct 21, 2016·Physics in Medicine and Biology·C Grassberger, H Paganetti
Mar 25, 2019·Bulletin of Mathematical Biology·Linnea C FranssenMark A J Chaplain
Oct 13, 2020·Frontiers in Oncology·Eleftheria TzamaliVangelis Sakkalis


Oct 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·Albert Goldbeter
Nov 1, 1985·Cell and Tissue Kinetics·L Hlatky, E L Alpen
Jun 1, 1980·Journal of Pharmacokinetics and Biopharmaceutics·V A LevinH D Landahl
May 29, 1997·The New England Journal of Medicine·J C Bailar, H L Gornik
Sep 18, 1998·Bulletin of Mathematical Biology·A R Anderson, Mark A J Chaplain
Mar 11, 1999·Current Opinion in Genetics & Development·M D Garrett, A Fattaey
Apr 4, 2000·Bio Systems·A R KansalThomas S Deisboeck
Sep 7, 2000·International Journal of Radiation Oncology, Biology, Physics·P F RijkenA J van der Kogel
Dec 12, 2000·The Journal of Biological Chemistry·L B GardnerC V Dang
May 24, 2001·Journal of Theoretical Biology·John J Tyson, Béla Novák
Dec 12, 2001·Journal of Theoretical Biology·A A PatelRobert A Gatenby
Jun 22, 2002·Journal of Theoretical Biology·Stephen Turner, Jonathan A Sherratt
Apr 19, 2003·The EMBO Journal·Guido SeriniFederico Bussolino
Sep 19, 2003·Antioxidants & Redox Signaling·Nobuhito GodaRandall S Johnson
Oct 1, 2003·Physics in Medicine and Biology·Alexandru DaşuMikael Karlsson
Dec 3, 2003·Biochemical Society Transactions·Béla Novák, John J Tyson
Feb 5, 2004·Journal of Theoretical Biology·Markus R OwenClaire E Lewis
Jul 6, 2004·Journal of Theoretical Biology·Tomás AlarcónPhilip K Maini
Sep 15, 2004·Journal of Theoretical Biology·Béla Novák, John J Tyson
Apr 28, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Marina VitaMoustapha Hassan
Dec 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gary K Schwartz, Manish A Shah
Apr 11, 2006·Journal of the American Psychoanalytic Association·Elizabeth Weinberg
May 26, 2006·Nature·Jacques PouysségurNathalie M Mazure
Mar 22, 2007·Journal of Theoretical Biology·Philip Gerlee, Alexander R A Anderson
Aug 19, 2007·Advanced Drug Delivery Reviews·Atilla AltinokAlbert Goldbeter
Dec 8, 2007·Journal of Mathematical Biology·Fadia Bekkal BrikciBenoît Perthame
Feb 14, 2008·IEEE Engineering in Medicine and Biology Magazine : the Quarterly Magazine of the Engineering in Medicine & Biology Society·Jean Clairambault
Sep 11, 2008·Journal of Mathematical Biology·John P SinekVittorio Cristini
Oct 8, 2008·Journal of Mathematical Biology·Alexander R A AndersonVito Quaranta
Oct 23, 2008·Journal of Mathematical Biology·Markus R OwenHelen M Byrne
Jul 15, 2009·Proceedings of the National Academy of Sciences of the United States of America·Anastasios MatzavinosAvner Friedman
Dec 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Claude Gérard, Albert Goldbeter
Feb 25, 2010·Nature Reviews. Cancer·Helen M Byrne
Apr 22, 2010·Biology Direct·Ariosto S Silva, Robert A Gatenby
Jun 10, 2010·Nature Reviews. Clinical Oncology·Eddy PasquierNicolas André
Sep 3, 2010·Nonlinearity·J S LowengrubVittorio Cristini
May 3, 2011·Annual Review of Biomedical Engineering·Thomas S DeisboeckVittorio Cristini
Mar 9, 2012·Computational and Mathematical Methods in Medicine·Gibin G PowathilSiv Sivaloganathan

Related Concepts

Metabolic Process, Cellular
In Silico
Tumor Cells, Uncertain Whether Benign or Malignant
Biochemical Pathway
Antineoplastic Agents
PLK1 gene
VHL protein, human
Angiogenic Process

Related Feeds

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.