Evolution of resistance during clonal expansion.

Genetics
Yoh IwasaFranziska Michor

Abstract

Acquired drug resistance is a major limitation for cancer therapy. Often, one genetic alteration suffices to confer resistance to an otherwise successful therapy. However, little is known about the dynamics of the emergence of resistant tumor cells. In this article, we consider an exponentially growing population starting from one cancer cell that is sensitive to therapy. Sensitive cancer cells can mutate into resistant ones, which have relative fitness alpha prior to therapy. In the special case of no cell death, our model converges to the one investigated by Luria and Delbrück. We calculate the probability of resistance and the mean number of resistant cells once the cancer has reached detection size M. The probability of resistance is an increasing function of the detection size M times the mutation rate u. If Mu << 1, then the expected number of resistant cells in cancers with resistance is independent of the mutation rate u and increases with M in proportion to M(1-1/alpha) for advantageous mutants with relative fitness alpha>1, to l nM for neutral mutants (alpha = 1), but converges to an upper limit for deleterious mutants (alpha<1). Further, the probability of resistance and the average number of resistant cells increase...Continue Reading

References

Nov 15, 1991·Science·M A NowakR M May
Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·T D TlstyK Lum
Apr 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·A G Knudson
May 22, 1997·Proceedings. Biological Sciences·S Bonhoeffer, M A Nowak
Jan 1, 1999·Nature·C LengauerB Vogelstein
Sep 6, 2000·Nature Medicine·C A SchmittS W Lowe
Apr 20, 2001·Nature·D D Richman
Aug 29, 2001·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·S B Levy
Nov 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Martin A NowakChristoph Lengauer
Dec 4, 2003·Journal of Theoretical Biology·Yoh IwasaMartin A Nowak
Jul 1, 2005·Nature·Franziska MichorMartin A Nowak
Nov 1, 1943·Genetics·S E Luria, M Delbrück

❮ Previous
Next ❯

Citations

Feb 9, 2012·Bulletin of Mathematical Biology·Cristian Tomasetti
Jul 12, 2011·The Lancet Oncology·Susanna L Cooke, James D Brenton
Sep 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Cristian Tomasetti, Doron Levy
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ivana BozicMartin A Nowak
Feb 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Christopher D McFarlandLeonid A Mirny
Jul 8, 2011·Science Translational Medicine·Juliann ChmieleckiWilliam Pao
Jul 11, 2013·PloS One·Hiroshi HaenoFranziska Michor
Dec 13, 2007·Genetics·Hiroshi HaenoFranziska Michor
Feb 9, 2012·International Journal of Molecular Sciences·Ruth ZarateJesús Garcia-Foncillas
Nov 17, 2010·Mathematical Biosciences and Engineering : MBE·Cristian Tomasetti, Doron Levy
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·David A Kessler, Herbert Levine
Apr 18, 2014·Nature Reviews. Cancer·Kirill S KorolevJeff Gore
Jul 31, 2013·Nucleic Acids Research·Francesco StrinoYuval Kluger
Oct 9, 2014·Systematic Biology·Niko BeerenwinkelFlorian Markowetz
Oct 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ivana Bozic, Martin A Nowak
Nov 4, 2015·Nature Reviews. Urology·Elizabeth Y Wei, James J Hsieh
Jan 25, 2007·Basic & Clinical Pharmacology & Toxicology·Sharon J OlijslagersMathieu H M Noteborn
Jun 12, 2013·Molecular Systems Biology·Bertram KlingerNils Blüthgen
Mar 24, 2016·Nature Reviews. Clinical Oncology·Leticia De Mattos-ArrudaJavier Cortés
Jun 26, 2015·ELife·Andrei R Akhmetzhanov, Michael E Hochberg
Jun 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Franziska Michor
Jun 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bruce M Boman, Max S Wicha
Apr 25, 2017·Scientific Reports·Francisco Martínez-JiménezMarc A Marti-Renom
May 23, 2017·Nature Communications·Prabir K ChakrabortyPriyabrata Mukherjee
Feb 20, 2007·Journal of Theoretical Biology·Hiroshi Haeno, Yoh Iwasa
Nov 10, 2009·Theoretical Population Biology·Richard Durrett, Stephen Moseley
Dec 3, 2014·Biochemical and Biophysical Research Communications·Yi-Fan ZhaoXiao-Jun Su
Oct 13, 2017·Bulletin of Mathematical Biology·Heyrim Cho, Doron Levy
Oct 31, 2017·PloS One·Ali Mahdipour-ShirayehSivabal Sivaloganathan
Feb 20, 2019·PLoS Computational Biology·Masayuki Maeda, Hideaki Yamashita
Jul 2, 2009·Annals of the New York Academy of Sciences·Camille Stephan-Otto Attolini, Franziska Michor
Jul 28, 2009·International Journal of Cancer. Journal International Du Cancer·Tongsen ZhengLianxin Liu
Oct 6, 2017·Briefings in Bioinformatics·Xiaoqiang Sun, Bin Hu
Nov 17, 2006·Nature Reviews. Cancer·Lauren M F MerloCarlo C Maley
Oct 13, 2006·British Journal of Cancer·L H Abbott, F Michor
Mar 23, 2019·JCO Clinical Cancer Informatics·Kimiyo N YamamotoFranziska Michor
Sep 24, 2015·Nature Communications·Sandra MisaleAlberto Bardelli

❮ Previous
Next ❯

Related Concepts

Related Feeds

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

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.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Natalia L Komarova, Dominik Wodarz
Proceedings. Biological Sciences
Yoh IwasaMartin A Nowak
© 2022 Meta ULC. All rights reserved