The role of chromosome missegregation in cancer development: a theoretical approach using agent-based modelling

PloS One
Arturo AraujoPeter Bentley

Abstract

Many cancers are aneuploid. However, the precise role that chromosomal instability plays in the development of cancer and in the response of tumours to treatment is still hotly debated. Here, to explore this question from a theoretical standpoint we have developed an agent-based model of tissue homeostasis in which to test the likely effects of whole chromosome mis-segregation during cancer development. In stochastic simulations, chromosome mis-segregation events at cell division lead to the generation of a diverse population of aneuploid clones that over time exhibit hyperplastic growth. Significantly, the course of cancer evolution depends on genetic linkage, as the structure of chromosomes lost or gained through mis-segregation events and the level of genetic instability function in tandem to determine the trajectory of cancer evolution. As a result, simulated cancers differ in their level of genetic stability and in their growth rates. We used this system to investigate the consequences of these differences in tumour heterogeneity for anti-cancer therapies based on surgery and anti-mitotic drugs that selectively target proliferating cells. As expected, simulated treatments induce a transient delay in tumour growth, and reve...Continue Reading

References

Aug 7, 1999·Stem Cells·D S Goodsell
Dec 28, 1999·American Journal of Surgery·H H LuuJ L Frank
Apr 3, 2001·Nature Reviews. Genetics·T Cremer, C Cremer
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Aug 29, 2003·Oncogene·Satoshi KanazawaB Matija Peterlin
Mar 3, 2004·Nature Reviews. Cancer·P Andrew FutrealMichael R Stratton
Apr 22, 2006·Cell Cycle·Charles SwantonJulian Downward
Aug 29, 2006·PLoS Computational Biology·Sabrina L SpencerStephanie Forrest
Sep 7, 2006·Artificial Life·Robert G AbbottKenneth J Pienta
Feb 27, 2007·Oncogene·H F Horn, K H Vousden
Apr 12, 2007·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, Edward D Salmon
Dec 7, 2007·Genes & Development·Robert Schneider, Rudolf Grosschedl
Apr 16, 2009·British Journal of Cancer·Charles Swanton, C Caldas
May 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Charles SwantonJulian Downward
Jun 24, 2009·Nature Reviews. Molecular Cell Biology·Andrew J Holland, Don W Cleveland
Oct 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Andrei SeluanovVera Gorbunova
Jan 23, 2010·Nature Reviews. Cancer·Juan-Manuel SchvartzmanR Benezra
Feb 19, 2010·Nature·Rameen BeroukhimMatthew Meyerson
Sep 18, 2010·Nature Reviews. Genetics·Matthew MeyersonGad Getz
Nov 4, 2010·Mathematical Biosciences·David BasantaAndreas Deutsch
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Jun 8, 2011·The Journal of Cell Biology·Robin M RickeJan M van Deursen
Sep 29, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Siobhán Q GreggLaura J Niedernhofer
Jan 25, 2012·Nature Reviews. Genetics·David J GordonDavid Pellman
Mar 9, 2012·The New England Journal of Medicine·Marco GerlingerCharles Swanton
Feb 24, 2016·Scientific Reports·Francisco SalinasFrancisco A Cubillos

Citations

May 6, 2014·Seminars in Cancer Biology·Zhihui WangThomas S Deisboeck
Sep 10, 2017·Journal of Translational Medicine·Albert Rübben, Arturo Araujo

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis