Tracking the evolution of cancer cell populations through the mathematical lens of phenotype-structured equations
Identifieur interne : 001516 ( Main/Exploration ); précédent : 001515; suivant : 001517Tracking the evolution of cancer cell populations through the mathematical lens of phenotype-structured equations
Auteurs : Tommaso Lorenzi ; Rebecca H. Chisholm [Australie] ; Jean Clairambault [France]Source :
- Biology Direct [ 1745-6150 ] ; 2016.
Abstract
A thorough understanding of the ecological and evolutionary mechanisms that drive the phenotypic evolution of neoplastic cells is a timely and key challenge for the cancer research community. In this respect, mathematical modelling can complement experimental cancer research by offering alternative means of understanding the results of in vitro and in vivo experiments, and by allowing for a quick and easy exploration of a variety of biological scenarios through
To elucidate the roles of phenotypic plasticity and selection pressures in tumour relapse, we present here a phenotype-structured model of evolutionary dynamics in a cancer cell population which is exposed to the action of a cytotoxic drug. The analytical tractability of our model allows us to investigate how the phenotype distribution, the level of phenotypic heterogeneity, and the size of the cell population are shaped by the strength of natural selection, the rate of random epimutations, the intensity of the competition for limited resources between cells, and the drug dose in use.
Our analytical results clarify the conditions for the successful adaptation of cancer cells faced with environmental changes. Furthermore, the results of our analyses demonstrate that the same cell population exposed to different concentrations of the same cytotoxic drug can take different evolutionary trajectories, which culminate in the selection of phenotypic variants characterised by different levels of drug tolerance. This suggests that the response of cancer cells to cytotoxic agents is more complex than a simple binary outcome,
This article was reviewed by Angela Pisco, Sébastien Benzekry and Heiko Enderling.
The online version of this article (doi:10.1186/s13062-016-0143-4) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s13062-016-0143-4
PubMed: 27550042
PubMed Central: 4994266
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000B30
- to stream Pmc, to step Curation: 000B07
- to stream Pmc, to step Checkpoint: 000514
- to stream PubMed, to step Corpus: 001A93
- to stream PubMed, to step Curation: 001A69
- to stream PubMed, to step Checkpoint: 001A69
- to stream Ncbi, to step Merge: 003A20
- to stream Ncbi, to step Curation: 003A20
- to stream Ncbi, to step Checkpoint: 003A20
- to stream Main, to step Merge: 001511
- to stream Main, to step Curation: 001516
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Tracking the evolution of cancer cell populations through the mathematical lens of phenotype-structured equations</title><author><name sortKey="Lorenzi, Tommaso" sort="Lorenzi, Tommaso" uniqKey="Lorenzi T" first="Tommaso" last="Lorenzi">Tommaso Lorenzi</name><affiliation><nlm:aff id="Aff1">School of Mathematics and Statistics, University of St Andrews, North Haugh, St Andrews, KY16 9SS UK</nlm:aff><wicri:noCountry code="subfield">KY16 9SS UK</wicri:noCountry></affiliation></author><author><name sortKey="Chisholm, Rebecca H" sort="Chisholm, Rebecca H" uniqKey="Chisholm R" first="Rebecca H." last="Chisholm">Rebecca H. Chisholm</name><affiliation wicri:level="3"><nlm:aff id="Aff2">School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW, Sydney, 2052 Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Clairambault, Jean" sort="Clairambault, Jean" uniqKey="Clairambault J" first="Jean" last="Clairambault">Jean Clairambault</name><affiliation wicri:level="3"><nlm:aff id="Aff3">INRIA Paris Research Centre, MAMBA team, 2, rue Simone Iff, CS 42112, Paris Cedex 12, 75589 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INRIA Paris Research Centre, MAMBA team, 2, rue Simone Iff, CS 42112, Paris Cedex 12</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">Sorbonne Universités, UPMC Univ. Paris 6, UMR 7598, Laboratoire Jacques-Louis Lions, Boîte courrier 187, 4 Place Jussieu, Paris Cedex 05, 75252 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC Univ. Paris 6, UMR 7598, Laboratoire Jacques-Louis Lions, Boîte courrier 187, 4 Place Jussieu, Paris Cedex 05</wicri:regionArea><wicri:noRegion>Paris Cedex 05</wicri:noRegion><wicri:noRegion>Paris Cedex 05</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27550042</idno><idno type="pmc">4994266</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994266</idno><idno type="RBID">PMC:4994266</idno><idno type="doi">10.1186/s13062-016-0143-4</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000B30</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B30</idno><idno type="wicri:Area/Pmc/Curation">000B07</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B07</idno><idno type="wicri:Area/Pmc/Checkpoint">000514</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000514</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">001A93</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001A93</idno><idno type="wicri:Area/PubMed/Curation">001A69</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001A69</idno><idno type="wicri:Area/PubMed/Checkpoint">001A69</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001A69</idno><idno type="wicri:Area/Ncbi/Merge">003A20</idno><idno type="wicri:Area/Ncbi/Curation">003A20</idno><idno type="wicri:Area/Ncbi/Checkpoint">003A20</idno><idno type="wicri:Area/Main/Merge">001511</idno><idno type="wicri:Area/Main/Curation">001516</idno><idno type="wicri:Area/Main/Exploration">001516</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Tracking the evolution of cancer cell populations through the mathematical lens of phenotype-structured equations</title><author><name sortKey="Lorenzi, Tommaso" sort="Lorenzi, Tommaso" uniqKey="Lorenzi T" first="Tommaso" last="Lorenzi">Tommaso Lorenzi</name><affiliation><nlm:aff id="Aff1">School of Mathematics and Statistics, University of St Andrews, North Haugh, St Andrews, KY16 9SS UK</nlm:aff><wicri:noCountry code="subfield">KY16 9SS UK</wicri:noCountry></affiliation></author><author><name sortKey="Chisholm, Rebecca H" sort="Chisholm, Rebecca H" uniqKey="Chisholm R" first="Rebecca H." last="Chisholm">Rebecca H. Chisholm</name><affiliation wicri:level="3"><nlm:aff id="Aff2">School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW, Sydney, 2052 Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Clairambault, Jean" sort="Clairambault, Jean" uniqKey="Clairambault J" first="Jean" last="Clairambault">Jean Clairambault</name><affiliation wicri:level="3"><nlm:aff id="Aff3">INRIA Paris Research Centre, MAMBA team, 2, rue Simone Iff, CS 42112, Paris Cedex 12, 75589 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INRIA Paris Research Centre, MAMBA team, 2, rue Simone Iff, CS 42112, Paris Cedex 12</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">Sorbonne Universités, UPMC Univ. Paris 6, UMR 7598, Laboratoire Jacques-Louis Lions, Boîte courrier 187, 4 Place Jussieu, Paris Cedex 05, 75252 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC Univ. Paris 6, UMR 7598, Laboratoire Jacques-Louis Lions, Boîte courrier 187, 4 Place Jussieu, Paris Cedex 05</wicri:regionArea><wicri:noRegion>Paris Cedex 05</wicri:noRegion><wicri:noRegion>Paris Cedex 05</wicri:noRegion></affiliation></author></analytic><series><title level="j">Biology Direct</title><idno type="eISSN">1745-6150</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>A thorough understanding of the ecological and evolutionary mechanisms that drive the phenotypic evolution of neoplastic cells is a timely and key challenge for the cancer research community. In this respect, mathematical modelling can complement experimental cancer research by offering alternative means of understanding the results of in vitro and in vivo experiments, and by allowing for a quick and easy exploration of a variety of biological scenarios through <italic>in silico</italic> studies.</p></sec><sec><title>Results</title><p>To elucidate the roles of phenotypic plasticity and selection pressures in tumour relapse, we present here a phenotype-structured model of evolutionary dynamics in a cancer cell population which is exposed to the action of a cytotoxic drug. The analytical tractability of our model allows us to investigate how the phenotype distribution, the level of phenotypic heterogeneity, and the size of the cell population are shaped by the strength of natural selection, the rate of random epimutations, the intensity of the competition for limited resources between cells, and the drug dose in use.</p></sec><sec><title>Conclusions</title><p>Our analytical results clarify the conditions for the successful adaptation of cancer cells faced with environmental changes. Furthermore, the results of our analyses demonstrate that the same cell population exposed to different concentrations of the same cytotoxic drug can take different evolutionary trajectories, which culminate in the selection of phenotypic variants characterised by different levels of drug tolerance. This suggests that the response of cancer cells to cytotoxic agents is more complex than a simple binary outcome, <italic>i.e.</italic>, extinction of sensitive cells and selection of highly resistant cells. Also, our mathematical results formalise the idea that the use of cytotoxic agents at high doses can act as a double-edged sword by promoting the outgrowth of drug resistant cellular clones. Overall, our theoretical work offers a formal basis for the development of anti-cancer therapeutic protocols that go beyond the ‘maximum-tolerated-dose paradigm’, as they may be more effective than traditional protocols at keeping the size of cancer cell populations under control while avoiding the expansion of drug tolerant clones.</p></sec><sec><title>Reviewers</title><p>This article was reviewed by Angela Pisco, Sébastien Benzekry and Heiko Enderling.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s13062-016-0143-4) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Aktipis, Ca" uniqKey="Aktipis C">CA Aktipis</name></author><author><name sortKey="Boddy, Am" uniqKey="Boddy A">AM Boddy</name></author><author><name sortKey="Gatenby, Ra" uniqKey="Gatenby R">RA Gatenby</name></author><author><name sortKey="Brown, Js" uniqKey="Brown J">JS Brown</name></author><author><name sortKey="Maley, Cc" uniqKey="Maley C">CC Maley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dexter, Dl" uniqKey="Dexter D">DL Dexter</name></author><author><name sortKey="Kowalski, Hm" uniqKey="Kowalski H">HM Kowalski</name></author><author><name sortKey="Blazar, Ba" uniqKey="Blazar B">BA Blazar</name></author><author><name sortKey="Fligiel, Z" uniqKey="Fligiel Z">Z Fligiel</name></author><author><name sortKey="Vogel, R" uniqKey="Vogel R">R Vogel</name></author><author><name sortKey="Heppner, Gh" uniqKey="Heppner G">GH Heppner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greaves, M" uniqKey="Greaves M">M Greaves</name></author><author><name sortKey="Maley, Cc" uniqKey="Maley C">CC Maley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Korolev, Ks" uniqKey="Korolev K">KS Korolev</name></author><author><name sortKey="Xavier, Jb" uniqKey="Xavier J">JB Xavier</name></author><author><name sortKey="Gore, J" uniqKey="Gore J">J Gore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Merlo, Lm" uniqKey="Merlo L">LM Merlo</name></author><author><name sortKey="Pepper, Jw" uniqKey="Pepper J">JW Pepper</name></author><author><name sortKey="Reid, Bj" uniqKey="Reid B">BJ Reid</name></author><author><name sortKey="Maley, Cc" uniqKey="Maley C">CC Maley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nowell, Pc" uniqKey="Nowell P">PC Nowell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marusyk, A" uniqKey="Marusyk A">A Marusyk</name></author><author><name sortKey="Almendro, V" uniqKey="Almendro V">V Almendro</name></author><author><name sortKey="Polyak, K" uniqKey="Polyak K">K Polyak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brock, A" uniqKey="Brock A">A Brock</name></author><author><name sortKey="Chang, H" uniqKey="Chang H">H Chang</name></author><author><name sortKey="Huang, S" uniqKey="Huang S">S Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Glasspool, R" uniqKey="Glasspool R">R Glasspool</name></author><author><name sortKey="Teodoridis, Jm" uniqKey="Teodoridis J">JM Teodoridis</name></author><author><name sortKey="Brown, R" uniqKey="Brown R">R Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gupta, Pb" uniqKey="Gupta P">PB Gupta</name></author><author><name sortKey="Fillmore, Cm" uniqKey="Fillmore C">CM Fillmore</name></author><author><name sortKey="Jiang, G" uniqKey="Jiang G">G Jiang</name></author><author><name sortKey="Shapira, Sd" uniqKey="Shapira S">SD Shapira</name></author><author><name sortKey="Tao, K" uniqKey="Tao K">K Tao</name></author><author><name sortKey="Kuperwasser, C" uniqKey="Kuperwasser C">C Kuperwasser</name></author><author><name sortKey="Lander, Es" uniqKey="Lander E">ES Lander</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Newman, Jr" uniqKey="Newman J">JR Newman</name></author><author><name sortKey="Ghaemmaghami, S" uniqKey="Ghaemmaghami S">S Ghaemmaghami</name></author><author><name sortKey="Ihmels, J" uniqKey="Ihmels J">J Ihmels</name></author><author><name sortKey="Breslow, Dk" uniqKey="Breslow D">DK Breslow</name></author><author><name sortKey="Noble, M" uniqKey="Noble M">M Noble</name></author><author><name sortKey="Derisi, Jl" uniqKey="Derisi J">JL DeRisi</name></author><author><name sortKey="Weissman, Js" uniqKey="Weissman J">JS Weissman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, A" uniqKey="Raj A">A Raj</name></author><author><name sortKey="Van Oudenaarden, A" uniqKey="Van Oudenaarden A">A van Oudenaarden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Hh" uniqKey="Chang H">HH Chang</name></author><author><name sortKey="Oh, Py" uniqKey="Oh P">PY Oh</name></author><author><name sortKey="Ingber, De" uniqKey="Ingber D">DE Ingber</name></author><author><name sortKey="Huang, S" uniqKey="Huang S">S Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pisco, Ao" uniqKey="Pisco A">AO Pisco</name></author><author><name sortKey="Brock, A" uniqKey="Brock A">A Brock</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J Zhou</name></author><author><name sortKey="Moor, A" uniqKey="Moor A">A Moor</name></author><author><name sortKey="Mojtahedi, M" uniqKey="Mojtahedi M">M Mojtahedi</name></author><author><name sortKey="Jackson, D" uniqKey="Jackson D">D Jackson</name></author><author><name sortKey="Huang, S" uniqKey="Huang S">S Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharma, Sv" uniqKey="Sharma S">SV Sharma</name></author><author><name sortKey="Lee, Dy" uniqKey="Lee D">DY Lee</name></author><author><name sortKey="Li, B" uniqKey="Li B">B Li</name></author><author><name sortKey="Quinlan, Mp" uniqKey="Quinlan M">MP Quinlan</name></author><author><name sortKey="Takahashi, F" uniqKey="Takahashi F">F Takahashi</name></author><author><name sortKey="Maheswaran, S" uniqKey="Maheswaran S">S Maheswaran</name></author><author><name sortKey="Mcdermott, U" uniqKey="Mcdermott U">U McDermott</name></author><author><name sortKey="Azizian, N" uniqKey="Azizian N">N Azizian</name></author><author><name sortKey="Zou, L" uniqKey="Zou L">L Zou</name></author><author><name sortKey="Fischbach, Ma" uniqKey="Fischbach M">MA Fischbach</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Huang, S" uniqKey="Huang S">S Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Altrock, Pm" uniqKey="Altrock P">PM Altrock</name></author><author><name sortKey="Liu, Ll" uniqKey="Liu L">LL Liu</name></author><author><name sortKey="Michor, F" uniqKey="Michor F">F Michor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anderson, Ar" uniqKey="Anderson A">AR Anderson</name></author><author><name sortKey="Quaranta, V" uniqKey="Quaranta V">V Quaranta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Byrne, Hm" uniqKey="Byrne H">HM Byrne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davies, P" uniqKey="Davies P">P Davies</name></author><author><name sortKey="Demetrius, L" uniqKey="Demetrius L">L Demetrius</name></author><author><name sortKey="Tuszynski, Ja" uniqKey="Tuszynski J">JA Tuszynski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Enderling, H" uniqKey="Enderling H">H Enderling</name></author><author><name sortKey="Aj Chaplain, M" uniqKey="Aj Chaplain M">M AJ Chaplain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Enderling, H" uniqKey="Enderling H">H Enderling</name></author><author><name sortKey="Rejniak, Ka" uniqKey="Rejniak K">KA Rejniak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gatenby, Ra" uniqKey="Gatenby R">RA Gatenby</name></author><author><name sortKey="Maini, Pk" uniqKey="Maini P">PK Maini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Powathil, Gg" uniqKey="Powathil G">GG Powathil</name></author><author><name sortKey="Swat, M" uniqKey="Swat M">M Swat</name></author><author><name sortKey="Chaplain, Ma" uniqKey="Chaplain M">MA Chaplain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stiehl, T" uniqKey="Stiehl T">T Stiehl</name></author><author><name sortKey="Baran, N" uniqKey="Baran N">N Baran</name></author><author><name sortKey="Ho, Ad" uniqKey="Ho A">AD Ho</name></author><author><name sortKey="Marciniak Czochra, A" uniqKey="Marciniak Czochra A">A Marciniak-Czochra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tuszynski, Ja" uniqKey="Tuszynski J">JA Tuszynski</name></author><author><name sortKey="Winter, P" uniqKey="Winter P">P Winter</name></author><author><name sortKey="White, D" uniqKey="White D">D White</name></author><author><name sortKey="Tseng, Cy" uniqKey="Tseng C">CY Tseng</name></author><author><name sortKey="Sahu, Kk" uniqKey="Sahu K">KK Sahu</name></author><author><name sortKey="Gentile, F" uniqKey="Gentile F">F Gentile</name></author><author><name sortKey="Spasevska, I" uniqKey="Spasevska I">I Spasevska</name></author><author><name sortKey="Omar, Si" uniqKey="Omar S">SI Omar</name></author><author><name sortKey="Nayebi, N" uniqKey="Nayebi N">N Nayebi</name></author><author><name sortKey="Churchill, Cd" uniqKey="Churchill C">CD Churchill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomas, F" uniqKey="Thomas F">F Thomas</name></author><author><name sortKey="Fisher, D" uniqKey="Fisher D">D Fisher</name></author><author><name sortKey="Fort, P" uniqKey="Fort P">P Fort</name></author><author><name sortKey="Marie, Jp" uniqKey="Marie J">JP Marie</name></author><author><name sortKey="Daoust, S" uniqKey="Daoust S">S Daoust</name></author><author><name sortKey="Roche, B" uniqKey="Roche B">B Roche</name></author><author><name sortKey="Grunau, C" uniqKey="Grunau C">C Grunau</name></author><author><name sortKey="Cosseau, C" uniqKey="Cosseau C">C Cosseau</name></author><author><name sortKey="Mitta, G" uniqKey="Mitta G">G Mitta</name></author><author><name sortKey="Baghdiguian, S" uniqKey="Baghdiguian S">S Baghdiguian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perthame, B" uniqKey="Perthame B">B Perthame</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perthame, B" uniqKey="Perthame B">B Perthame</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Champagnat, N" uniqKey="Champagnat N">N Champagnat</name></author><author><name sortKey="Ferriere, R" uniqKey="Ferriere R">R Ferrière</name></author><author><name sortKey="Ben Arous, G" uniqKey="Ben Arous G">G Ben Arous</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Champagnat, N" uniqKey="Champagnat N">N Champagnat</name></author><author><name sortKey="Ferriere, R" uniqKey="Ferriere R">R Ferrière</name></author><author><name sortKey="Meleard, S" uniqKey="Meleard S">S Méléard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chisholm, Rh" uniqKey="Chisholm R">RH Chisholm</name></author><author><name sortKey="Lorenzi, T" uniqKey="Lorenzi T">T Lorenzi</name></author><author><name sortKey="Desvillettes, L" uniqKey="Desvillettes L">L Desvillettes</name></author><author><name sortKey="Hughes, Bd" uniqKey="Hughes B">BD Hughes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clairambault, J" uniqKey="Clairambault J">J Clairambault</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lorz, A" uniqKey="Lorz A">A Lorz</name></author><author><name sortKey="Lorenzi, T" uniqKey="Lorenzi T">T Lorenzi</name></author><author><name sortKey="Hochberg, Me" uniqKey="Hochberg M">ME Hochberg</name></author><author><name sortKey="Clairambault, J" uniqKey="Clairambault J">J Clairambault</name></author><author><name sortKey="Perthame, B" uniqKey="Perthame B">B Perthame</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lorz, A" uniqKey="Lorz A">A Lorz</name></author><author><name sortKey="Lorenzi, T" uniqKey="Lorenzi T">T Lorenzi</name></author><author><name sortKey="Clairambault, J" uniqKey="Clairambault J">J Clairambault</name></author><author><name sortKey="Escargueil, A" uniqKey="Escargueil A">A Escargueil</name></author><author><name sortKey="Perthame, B" uniqKey="Perthame B">B Perthame</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chisholm, Rh" uniqKey="Chisholm R">RH Chisholm</name></author><author><name sortKey="Lorenzi, T" uniqKey="Lorenzi T">T Lorenzi</name></author><author><name sortKey="Lorz, A" uniqKey="Lorz A">A Lorz</name></author><author><name sortKey="Larsen, Ak" uniqKey="Larsen A">AK Larsen</name></author><author><name sortKey="De Almeida, Ln" uniqKey="De Almeida L">LN De Almeida</name></author><author><name sortKey="Escargueil, A" uniqKey="Escargueil A">A Escargueil</name></author><author><name sortKey="Clairambault, J" uniqKey="Clairambault J">J Clairambault</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pisco, A" uniqKey="Pisco A">A Pisco</name></author><author><name sortKey="Huang, S" uniqKey="Huang S">S Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hanahan, D" uniqKey="Hanahan D">D Hanahan</name></author><author><name sortKey="Weinberg, Ra" uniqKey="Weinberg R">RA Weinberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Medema, Jp" uniqKey="Medema J">JP Medema</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menendez, Ja" uniqKey="Menendez J">JA Menendez</name></author><author><name sortKey="Alarc N, T" uniqKey="Alarc N T">T Alarcón</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lorenzi, T" uniqKey="Lorenzi T">T Lorenzi</name></author><author><name sortKey="Chisholm, Rh" uniqKey="Chisholm R">RH Chisholm</name></author><author><name sortKey="Desvillettes, L" uniqKey="Desvillettes L">L Desvillettes</name></author><author><name sortKey="Hughes, Bd" uniqKey="Hughes B">BD Hughes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chisholm, Rh" uniqKey="Chisholm R">RH Chisholm</name></author><author><name sortKey="Lorenzi, T" uniqKey="Lorenzi T">T Lorenzi</name></author><author><name sortKey="Lorz, A" uniqKey="Lorz A">A Lorz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Becker, C" uniqKey="Becker C">C Becker</name></author><author><name sortKey="Hagmann, J" uniqKey="Hagmann J">J Hagmann</name></author><author><name sortKey="Muller, J" uniqKey="Muller J">J Müller</name></author><author><name sortKey="Koenig, D" uniqKey="Koenig D">D Koenig</name></author><author><name sortKey="Stegle, O" uniqKey="Stegle O">O Stegle</name></author><author><name sortKey="Borgwardt, K" uniqKey="Borgwardt K">K Borgwardt</name></author><author><name sortKey="Weigel, D" uniqKey="Weigel D">D Weigel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Navin, Ne" uniqKey="Navin N">NE Navin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leveque, Rj" uniqKey="Leveque R">RJ LeVeque</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steel, G" uniqKey="Steel G">G Steel</name></author><author><name sortKey="Lamerton, L" uniqKey="Lamerton L">L Lamerton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bozic, I" uniqKey="Bozic I">I Bozic</name></author><author><name sortKey="Reiter, Jg" uniqKey="Reiter J">JG Reiter</name></author><author><name sortKey="Allen, B" uniqKey="Allen B">B Allen</name></author><author><name sortKey="Antal, T" uniqKey="Antal T">T Antal</name></author><author><name sortKey="Chatterjee, K" uniqKey="Chatterjee K">K Chatterjee</name></author><author><name sortKey="Shah, P" uniqKey="Shah P">P Shah</name></author><author><name sortKey="Moon, Ys" uniqKey="Moon Y">YS Moon</name></author><author><name sortKey="Yaqubie, A" uniqKey="Yaqubie A">A Yaqubie</name></author><author><name sortKey="Kelly, N" uniqKey="Kelly N">N Kelly</name></author><author><name sortKey="Le, Dt" uniqKey="Le D">DT Le</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bozic, I" uniqKey="Bozic I">I Bozic</name></author><author><name sortKey="Allen, B" uniqKey="Allen B">B Allen</name></author><author><name sortKey="Nowak, Ma" uniqKey="Nowak M">MA Nowak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gately, S" uniqKey="Gately S">S Gately</name></author><author><name sortKey="Kerbel, R" uniqKey="Kerbel R">R Kerbel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cohen, Aa" uniqKey="Cohen A">AA Cohen</name></author><author><name sortKey="Geva Zatorsky, N" uniqKey="Geva Zatorsky N">N Geva-Zatorsky</name></author><author><name sortKey="Eden, E" uniqKey="Eden E">E Eden</name></author><author><name sortKey="Frenkel Morgenstern, M" uniqKey="Frenkel Morgenstern M">M Frenkel-Morgenstern</name></author><author><name sortKey="Issaeva, I" uniqKey="Issaeva I">I Issaeva</name></author><author><name sortKey="Sigal, A" uniqKey="Sigal A">A Sigal</name></author><author><name sortKey="Milo, R" uniqKey="Milo R">R Milo</name></author><author><name sortKey="Cohen Saidon, C" uniqKey="Cohen Saidon C">C Cohen-Saidon</name></author><author><name sortKey="Liron, Y" uniqKey="Liron Y">Y Liron</name></author><author><name sortKey="Kam, Z" uniqKey="Kam Z">Z Kam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delitala, M" uniqKey="Delitala M">M Delitala</name></author><author><name sortKey="Lorenzi, T" uniqKey="Lorenzi T">T Lorenzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delitala, M" uniqKey="Delitala M">M Delitala</name></author><author><name sortKey="Lorenzi, T" uniqKey="Lorenzi T">T Lorenzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="J Nne, Pa" uniqKey="J Nne P">PA Jänne</name></author><author><name sortKey="Gray, N" uniqKey="Gray N">N Gray</name></author><author><name sortKey="Settleman, J" uniqKey="Settleman J">J Settleman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lavi, O" uniqKey="Lavi O">O Lavi</name></author><author><name sortKey="Greene, Jm" uniqKey="Greene J">JM Greene</name></author><author><name sortKey="Levy, D" uniqKey="Levy D">D Levy</name></author><author><name sortKey="Gottesman, Mm" uniqKey="Gottesman M">MM Gottesman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spencer, Sl" uniqKey="Spencer S">SL Spencer</name></author><author><name sortKey="Gaudet, S" uniqKey="Gaudet S">S Gaudet</name></author><author><name sortKey="Albeck, Jg" uniqKey="Albeck J">JG Albeck</name></author><author><name sortKey="Burke, Jm" uniqKey="Burke J">JM Burke</name></author><author><name sortKey="Sorger, Pk" uniqKey="Sorger P">PK Sorger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Bruin, Ec" uniqKey="De Bruin E">EC De Bruin</name></author><author><name sortKey="Taylor, Tb" uniqKey="Taylor T">TB Taylor</name></author><author><name sortKey="Swanton, C" uniqKey="Swanton C">C Swanton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Acar, M" uniqKey="Acar M">M Acar</name></author><author><name sortKey="Mettetal, Jt" uniqKey="Mettetal J">JT Mettetal</name></author><author><name sortKey="Van Oudenaarden, A" uniqKey="Van Oudenaarden A">A van Oudenaarden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerlinger, M" uniqKey="Gerlinger M">M Gerlinger</name></author><author><name sortKey="Rowan, Aj" uniqKey="Rowan A">AJ Rowan</name></author><author><name sortKey="Horswell, S" uniqKey="Horswell S">S Horswell</name></author><author><name sortKey="Larkin, J" uniqKey="Larkin J">J Larkin</name></author><author><name sortKey="Endesfelder, D" uniqKey="Endesfelder D">D Endesfelder</name></author><author><name sortKey="Gronroos, E" uniqKey="Gronroos E">E Gronroos</name></author><author><name sortKey="Martinez, P" uniqKey="Martinez P">P Martinez</name></author><author><name sortKey="Matthews, N" uniqKey="Matthews N">N Matthews</name></author><author><name sortKey="Stewart, A" uniqKey="Stewart A">A Stewart</name></author><author><name sortKey="Tarpey, P" uniqKey="Tarpey P">P Tarpey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Minchinton, Ai" uniqKey="Minchinton A">AI Minchinton</name></author><author><name sortKey="Tannock, If" uniqKey="Tannock I">IF Tannock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tredan, O" uniqKey="Tredan O">O Trédan</name></author><author><name sortKey="Galmarini, Cm" uniqKey="Galmarini C">CM Galmarini</name></author><author><name sortKey="Patel, K" uniqKey="Patel K">K Patel</name></author><author><name sortKey="Tannock, If" uniqKey="Tannock I">IF Tannock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, C" uniqKey="Sun C">C Sun</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Huang, S" uniqKey="Huang S">S Huang</name></author><author><name sortKey="Heynen, Gj" uniqKey="Heynen G">GJ Heynen</name></author><author><name sortKey="Prahallad, A" uniqKey="Prahallad A">A Prahallad</name></author><author><name sortKey="Robert, C" uniqKey="Robert C">C Robert</name></author><author><name sortKey="Haanen, J" uniqKey="Haanen J">J Haanen</name></author><author><name sortKey="Blank, C" uniqKey="Blank C">C Blank</name></author><author><name sortKey="Wesseling, J" uniqKey="Wesseling J">J Wesseling</name></author><author><name sortKey="Willems, Sm" uniqKey="Willems S">SM Willems</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andre, N" uniqKey="Andre N">N André</name></author><author><name sortKey="Carre, M" uniqKey="Carre M">M Carré</name></author><author><name sortKey="Pasquier, E" uniqKey="Pasquier E">E Pasquier</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Hanahan, D" uniqKey="Hanahan D">D Hanahan</name></author><author><name sortKey="Bergers, G" uniqKey="Bergers G">G Bergers</name></author><author><name sortKey="Bergsland, E" uniqKey="Bergsland E">E Bergsland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scharovsky, Og" uniqKey="Scharovsky O">OG Scharovsky</name></author><author><name sortKey="Mainetti, Le" uniqKey="Mainetti L">LE Mainetti</name></author><author><name sortKey="Rozados, Vr" uniqKey="Rozados V">VR Rozados</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gatenby, Ra" uniqKey="Gatenby R">RA Gatenby</name></author><author><name sortKey="Silva, As" uniqKey="Silva A">AS Silva</name></author><author><name sortKey="Gillies, Rj" uniqKey="Gillies R">RJ Gillies</name></author><author><name sortKey="Frieden, Br" uniqKey="Frieden B">BR Frieden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bremnes, Rm" uniqKey="Bremnes R">RM Bremnes</name></author><author><name sortKey="D Nnem, T" uniqKey="D Nnem T">T Dønnem</name></author><author><name sortKey="Al Saad, S" uniqKey="Al Saad S">S Al-Saad</name></author><author><name sortKey="Al Shibli, K" uniqKey="Al Shibli K">K Al-Shibli</name></author><author><name sortKey="Andersen, S" uniqKey="Andersen S">S Andersen</name></author><author><name sortKey="Sirera, R" uniqKey="Sirera R">R Sirera</name></author><author><name sortKey="Camps, C" uniqKey="Camps C">C Camps</name></author><author><name sortKey="Marinez, I" uniqKey="Marinez I">I Marinez</name></author><author><name sortKey="Busund, Lt" uniqKey="Busund L">LT Busund</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cirri, P" uniqKey="Cirri P">P Cirri</name></author><author><name sortKey="Chiarugi, P" uniqKey="Chiarugi P">P Chiarugi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mao, Y" uniqKey="Mao Y">Y Mao</name></author><author><name sortKey="Keller, Et" uniqKey="Keller E">ET Keller</name></author><author><name sortKey="Garfield, Dh" uniqKey="Garfield D">DH Garfield</name></author><author><name sortKey="Shen, K" uniqKey="Shen K">K Shen</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nieman, Km" uniqKey="Nieman K">KM Nieman</name></author><author><name sortKey="Kenny, Ha" uniqKey="Kenny H">HA Kenny</name></author><author><name sortKey="Penicka, Cv" uniqKey="Penicka C">CV Penicka</name></author><author><name sortKey="Ladanyi, A" uniqKey="Ladanyi A">A Ladanyi</name></author><author><name sortKey="Buell Gutbrod, R" uniqKey="Buell Gutbrod R">R Buell-Gutbrod</name></author><author><name sortKey="Zillhardt, Mr" uniqKey="Zillhardt M">MR Zillhardt</name></author><author><name sortKey="Romero, Il" uniqKey="Romero I">IL Romero</name></author><author><name sortKey="Carey, Ms" uniqKey="Carey M">MS Carey</name></author><author><name sortKey="Mills, Gb" uniqKey="Mills G">GB Mills</name></author><author><name sortKey="Hotamisligil, Gs" uniqKey="Hotamisligil G">GS Hotamisligil</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mendoza Juez, B" uniqKey="Mendoza Juez B">B Mendoza-Juez</name></author><author><name sortKey="Martinez Gonzalez, A" uniqKey="Martinez Gonzalez A">A Martínez-González</name></author><author><name sortKey="Calvo, Gf" uniqKey="Calvo G">GF Calvo</name></author><author><name sortKey="Perez Garcia, Vm" uniqKey="Perez Garcia V">VM Pérez-García</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smallbone, K" uniqKey="Smallbone K">K Smallbone</name></author><author><name sortKey="Gatenby, Ra" uniqKey="Gatenby R">RA Gatenby</name></author><author><name sortKey="Gillies, Rj" uniqKey="Gillies R">RJ Gillies</name></author><author><name sortKey="Maini, Pk" uniqKey="Maini P">PK Maini</name></author><author><name sortKey="Gavaghan, Dj" uniqKey="Gavaghan D">DJ Gavaghan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goding, Cr" uniqKey="Goding C">CR Goding</name></author><author><name sortKey="Pei, D" uniqKey="Pei D">D Pei</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delhommeau, F" uniqKey="Delhommeau F">F Delhommeau</name></author><author><name sortKey="Dupont, S" uniqKey="Dupont S">S Dupont</name></author><author><name sortKey="Della Valle, V" uniqKey="Della Valle V">V Della Valle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Solary, E" uniqKey="Solary E">E Solary</name></author><author><name sortKey="Bernard, Oa" uniqKey="Bernard O">OA Bernard</name></author><author><name sortKey="Tefferi, A" uniqKey="Tefferi A">A Tefferi</name></author><author><name sortKey="Fuks, F" uniqKey="Fuks F">F Fuks</name></author><author><name sortKey="Vainchenker, W" uniqKey="Vainchenker W">W Vainchenker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, J" uniqKey="Miller J">J Miller</name></author></analytic></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Nouvelle-Galles du Sud</li><li>Rhône-Alpes</li></region><settlement><li>Paris</li><li>Sydney</li></settlement></list><tree><noCountry><name sortKey="Lorenzi, Tommaso" sort="Lorenzi, Tommaso" uniqKey="Lorenzi T" first="Tommaso" last="Lorenzi">Tommaso Lorenzi</name></noCountry><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Chisholm, Rebecca H" sort="Chisholm, Rebecca H" uniqKey="Chisholm R" first="Rebecca H." last="Chisholm">Rebecca H. Chisholm</name></region></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Clairambault, Jean" sort="Clairambault, Jean" uniqKey="Clairambault J" first="Jean" last="Clairambault">Jean Clairambault</name></region><name sortKey="Clairambault, Jean" sort="Clairambault, Jean" uniqKey="Clairambault J" first="Jean" last="Clairambault">Jean Clairambault</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001516 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001516 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:4994266
|texte= Tracking the evolution of cancer cell populations through the mathematical lens of phenotype-structured equations
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:27550042" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |