<?xml version='1.0' encoding='UTF-8' standalone='no'?>
<sbml xmlns="http://www.sbml.org/sbml/level3/version1/core" layout:required="false" level="3" render:required="false" version="1" xmlns:layout="http://www.sbml.org/sbml/level3/version1/layout/version1" xmlns:render="http://www.sbml.org/sbml/level3/version1/render/version1">
  <model areaUnits="area" extentUnits="substance" id="Monro2008___chemotherapy_resistance" lengthUnits="length" metaid="COPASI0" name="Monro2008 - chemotherapy resistance" substanceUnits="substance" timeUnits="time" volumeUnits="volume">
    <notes>
      <body xmlns="http://www.w3.org/1999/xhtml">
     <p>The paper describes a model of resistance of cancer to chemotherapy. 
Created by COPASI 4.25 (Build 207) 

This model is described in the article: 
Modelling chemotherapy resistance in palliation and failed cure 
Helen C. Monro, Eamonn A. Gaffney 
J Theor Biol. 2009, 257 (2), pp.292 

Abstract: 

The goal of palliative cancer chemotherapy treatment is to prolong survival and improve quality of life when tumour eradication is not feasible. Chemotherapy protocol design is considered in this context using a simple, robust, model of advanced tumour growth with Gompertzian dynamics, taking into account the effects of drug resistance. It is predicted that reduced chemotherapy protocols can readily lead to improved survival times due to the effects of competition between resistant and sensitive tumour cells. Very early palliation is also predicted to quickly yield near total tumour resistance and thus decrease survival duration. Finally, our simulations indicate that failed curative attempts using dose densification, a common protocol escalation strategy, can reduce survival times.

To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . 
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. 
Please refer to CC0 Public Domain Dedication for more information.</p>
  </body>
    </notes>
    <annotation>
      <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
        <rdf:Description rdf:about="#COPASI0">
          <dcterms:creator>
            <rdf:Bag>
              <rdf:li rdf:parseType="Resource">
                <vCard:N rdf:parseType="Resource">
                  <vCard:Family>Men</vCard:Family>
                  <vCard:Given>Jinghao</vCard:Given>
                </vCard:N>
                <vCard:EMAIL>jm2187@cam.ac.uk</vCard:EMAIL>
                <vCard:ORG rdf:parseType="Resource">
                  <vCard:Orgname>University of Cambridge</vCard:Orgname>
                </vCard:ORG>
              </rdf:li>
            </rdf:Bag>
          </dcterms:creator>
	<dcterms:created rdf:parseType="Resource">
	<dcterms:W3CDTF>2019-08-02T14:25:20Z</dcterms:W3CDTF>
	</dcterms:created>
	<dcterms:modified rdf:parseType="Resource">
	<dcterms:W3CDTF>2019-08-02T14:25:20Z</dcterms:W3CDTF>
	</dcterms:modified>
	<bqmodel:isDescribedBy>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/pubmed/19135065"/>
	</rdf:Bag>
	</bqmodel:isDescribedBy>
	<bqbiol:hasProperty>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C15632"/>
	</rdf:Bag>
	</bqbiol:hasProperty>
	<bqbiol:hasProperty>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/mamo/MAMO_0000046"/>
	</rdf:Bag>
	</bqbiol:hasProperty>
	<bqbiol:hasTaxon>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/taxonomy/9606"/>
	</rdf:Bag>
	</bqbiol:hasTaxon>
	<bqmodel:is>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/biomodels.db/MODEL1908020002"/>
	<rdf:li rdf:resource="http://identifiers.org/biomodels.db/BIOMD0000000776"/>
	</rdf:Bag>
	</bqmodel:is>
	</rdf:Description>
      </rdf:RDF>
      <COPASI xmlns="http://www.copasi.org/static/sbml">
        <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
          <rdf:Description rdf:about="#COPASI0">
            <bqbiol:hasProperty rdf:resource="urn:miriam:mamo:MAMO_0000046"/>
            <bqbiol:hasProperty rdf:resource="urn:miriam:ncit:C15632"/>
            <bqbiol:hasTaxon rdf:resource="urn:miriam:taxonomy:9606"/>
            <dcterms:bibliographicCitation>
              <rdf:Description>
                <CopasiMT:isDescribedBy rdf:resource="urn:miriam:pubmed:19135065"/>
              </rdf:Description>
            </dcterms:bibliographicCitation>
            <dcterms:created>
              <rdf:Description>
                <dcterms:W3CDTF>2019-08-02T14:25:20Z</dcterms:W3CDTF>
              </rdf:Description>
            </dcterms:created>
            <dcterms:creator>
              <rdf:Description>
                <vCard:EMAIL>jm2187@cam.ac.uk</vCard:EMAIL>
                <vCard:N>
                  <rdf:Description>
                    <vCard:Family>Men</vCard:Family>
                    <vCard:Given>Jinghao</vCard:Given>
                  </rdf:Description>
                </vCard:N>
                <vCard:ORG>
                  <rdf:Description>
                    <vCard:Orgname>University of Cambridge</vCard:Orgname>
                  </rdf:Description>
                </vCard:ORG>
              </rdf:Description>
            </dcterms:creator>
          </rdf:Description>
        </rdf:RDF>
      </COPASI>
    </annotation>
      <listOfFunctionDefinitions>
      <functionDefinition id="resistance_0" metaid="COPASI15" name="resistance">
        <annotation>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI15">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:40:59Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
        <math xmlns="http://www.w3.org/1998/Math/MathML">        
          <lambda>
            <bvar>
              <ci> t1 </ci>
            </bvar>
            <bvar>
              <ci> S </ci>
            </bvar>
            <bvar>
              <ci> t2 </ci>
            </bvar>
            <bvar>
              <ci> R </ci>
            </bvar>
            <bvar>
              <ci> b </ci>
            </bvar>
            <bvar>
              <ci> N </ci>
            </bvar>
            <bvar>
              <ci> Ninf </ci>
            </bvar>
            <apply>
              <times/>
              <apply>
                <minus/>
                <ci> b </ci>
              </apply>
              <apply>
                <ln/>
                <apply>
                  <divide/>
                  <ci> N </ci>
                  <ci> Ninf </ci>
                </apply>
              </apply>
              <apply>
                <minus/>
                <apply>
                  <times/>
                  <ci> t1 </ci>
                  <ci> S </ci>
                </apply>
                <apply>
                  <times/>
                  <ci> t2 </ci>
                  <ci> R </ci>
                </apply>
              </apply>
            </apply>
          </lambda>
        </math>
            </functionDefinition>
      <functionDefinition id="sd" metaid="COPASI16" name="sd">
        <annotation>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI16">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:38:51Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
        <math xmlns="http://www.w3.org/1998/Math/MathML">        
          <lambda>
            <bvar>
              <ci> b </ci>
            </bvar>
            <bvar>
              <ci> N </ci>
            </bvar>
            <bvar>
              <ci> Ninf </ci>
            </bvar>
            <bvar>
              <ci> C0 </ci>
            </bvar>
            <bvar>
              <ci> S </ci>
            </bvar>
            <apply>
              <times/>
              <apply>
                <minus/>
                <ci> b </ci>
              </apply>
              <apply>
                <ln/>
                <apply>
                  <divide/>
                  <ci> N </ci>
                  <ci> Ninf </ci>
                </apply>
              </apply>
              <ci> C0 </ci>
              <ci> S </ci>
            </apply>
          </lambda>
        </math>
            </functionDefinition>
      <functionDefinition id="growth" metaid="COPASI17" name="growth">
        <annotation>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI17">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:38:08Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
        <math xmlns="http://www.w3.org/1998/Math/MathML">        
          <lambda>
            <bvar>
              <ci> b </ci>
            </bvar>
            <bvar>
              <ci> N </ci>
            </bvar>
            <bvar>
              <ci> Ninf </ci>
            </bvar>
            <bvar>
              <ci> pro </ci>
            </bvar>
            <apply>
              <times/>
              <apply>
                <minus/>
                <ci> b </ci>
              </apply>
              <apply>
                <ln/>
                <apply>
                  <divide/>
                  <ci> N </ci>
                  <ci> Ninf </ci>
                </apply>
              </apply>
              <ci> pro </ci>
            </apply>
          </lambda>
        </math>
            </functionDefinition>
    </listOfFunctionDefinitions>
    <listOfUnitDefinitions>
      <unitDefinition id="length" name="length">
        <listOfUnits>
          <unit exponent="1" kind="metre" multiplier="1" scale="0"/>
        </listOfUnits>
      </unitDefinition>
      <unitDefinition id="area" name="area">
        <listOfUnits>
          <unit exponent="2" kind="metre" multiplier="1" scale="0"/>
        </listOfUnits>
      </unitDefinition>
      <unitDefinition id="volume" name="volume">
        <listOfUnits>
          <unit exponent="1" kind="litre" multiplier="1" scale="-3"/>
        </listOfUnits>
      </unitDefinition>
      <unitDefinition id="time" name="time">
        <listOfUnits>
          <unit exponent="1" kind="second" multiplier="86400" scale="0"/>
        </listOfUnits>
      </unitDefinition>
      <unitDefinition id="substance" name="substance">
        <listOfUnits>
          <unit exponent="1" kind="mole" multiplier="1" scale="-3"/>
        </listOfUnits>
      </unitDefinition>
      <unitDefinition id="unit_0" name="1/d">
        <listOfUnits>
          <unit exponent="-1" kind="second" multiplier="86400" scale="-1"/>
        </listOfUnits>
      </unitDefinition>
      <unitDefinition id="unit_1" name="1">
        <listOfUnits>
          <unit exponent="0" kind="dimensionless" multiplier="1" scale="0"/>
        </listOfUnits>
      </unitDefinition>
    </listOfUnitDefinitions>
    <listOfCompartments>
      <compartment constant="true" id="tme" metaid="COPASI1" name="tme" size="1" spatialDimensions="3" units="volume">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI1">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C94498"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI1">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:29:51Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:ncit:C94498"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </compartment>
    </listOfCompartments>
    <listOfSpecies>
      <species boundaryCondition="false" compartment="tme" constant="false" hasOnlySubstanceUnits="false" id="S" initialConcentration="1E10" metaid="COPASI2" name="S" substanceUnits="substance">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
            <pre>sensitive cell</pre>
          </body>
        </notes>
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI2">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/cl/CL:0001064"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI2">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:30:16Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:cl:CL:0001064"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </species>
      <species boundaryCondition="false" compartment="tme" constant="false" hasOnlySubstanceUnits="false" id="R" initialConcentration="200000" metaid="COPASI3" name="R" substanceUnits="substance">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
            <pre>resistant cell</pre>
          </body>
        </notes>
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI3">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/cl/CL:0001064"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI3">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:30:18Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:cl:CL:0001064"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </species>
    </listOfSpecies>
    <listOfParameters>
      <parameter constant="true" id="b" metaid="COPASI4" name="b" units="unit_0" value="0.005928">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
            <pre>Rate of growth retardation
0.005928/d=2.47e-4/h</pre>
          </body>
        </notes>
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI4">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C25636"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI4">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:30:24Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:ncit:C25636"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </parameter>
      <parameter constant="false" id="N" metaid="COPASI5" name="N" units="unit_1" value="1.00002E10">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
            <pre>total number of cells</pre>
          </body>
        </notes>
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI5">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/cl/CL:0001064"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI5">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:30:30Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:cl:CL:0001064"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </parameter>
      <parameter constant="true" id="C0" metaid="COPASI6" name="C0" units="unit_1" value="2">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
            <pre>Level of chemotherapy cell kill, 0-40
=0/0.74/0.9/2</pre>
          </body>
        </notes>
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI6">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C48922"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI6">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:30:34Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:ncit:C48922"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </parameter>
      <parameter constant="true" id="t1" metaid="COPASI7" name="t1" units="unit_1" value="1E-6">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
            <pre>Mutation to resistance per cell cycle</pre>
          </body>
        </notes>
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI7">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C25636"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI7">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:30:35Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:ncit:C25636"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </parameter>
      <parameter constant="true" id="t2" metaid="COPASI8" name="t2" units="unit_1" value="1E-6">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
            <pre>Back-mutation to sensitivity per cell cycle</pre>
          </body>
        </notes>
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI8">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C25636"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI8">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:30:37Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:ncit:C25636"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </parameter>
      <parameter constant="true" id="Ninf" metaid="COPASI9" name="Ninf" units="unit_1" value="2E12">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
            <pre>Saturating number of cells in absence of therapy</pre>
          </body>
        </notes>
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI9">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/sbo/SBO:0000661"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI9">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:30:57Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:sbo:SBO:0000661"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </parameter>
      <parameter constant="true" id="Ncrit" metaid="COPASI10" name="Ncrit" units="unit_1" value="5E11">
        <notes>
          <body xmlns="http://www.w3.org/1999/xhtml">
            <pre>Critical (fatal) number of cells, tumor diameter=10cm</pre>
          </body>
        </notes>
        <annotation>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI10">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:32:55Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
            </parameter>
    </listOfParameters>
    <listOfRules>
      <assignmentRule variable="N">
        <math xmlns="http://www.w3.org/1998/Math/MathML">        
          <apply>
            <plus/>
            <ci> R </ci>
            <ci> S </ci>
          </apply>
        </math>
            </assignmentRule>
    </listOfRules>
    <listOfReactions>
      <reaction fast="false" id="sensitive_cell_growth" metaid="COPASI11" name="sensitive cell growth" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI11">
              <bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/sbo/SBO:0000393"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/go/GO:0000828"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI11">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:36:03Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:go:GO:000828"/>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:sbo:SBO:0000393"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfProducts>
          <speciesReference constant="true" species="S" stoichiometry="1"/>
        </listOfProducts>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> tme </ci>
              <apply>
                <ci> growth </ci>
                <ci> b </ci>
                <ci> N </ci>
                <ci> Ninf </ci>
                <ci> S </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction fast="false" id="sensitive_cell_death" metaid="COPASI12" name="sensitive cell death" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI12">
              <bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/go/GO:0008219"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/sbo/SBO:0000179"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI12">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:36:10Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:go:GO:0008219"/>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:sbo:SBO:0000179"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfReactants>
          <speciesReference constant="true" species="S" stoichiometry="1"/>
        </listOfReactants>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> tme </ci>
              <apply>
                <ci> sd </ci>
                <ci> b </ci>
                <ci> N </ci>
                <ci> Ninf </ci>
                <ci> C0 </ci>
                <ci> S </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction fast="false" id="resistance" metaid="COPASI13" name="resistance" reversible="true">
        <annotation>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI13">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:36:17Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfReactants>
          <speciesReference constant="true" species="S" stoichiometry="1"/>
        </listOfReactants>
        <listOfProducts>
          <speciesReference constant="true" species="R" stoichiometry="1"/>
        </listOfProducts>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> tme </ci>
              <apply>
                <ci> resistance_0 </ci>
                <ci> t1 </ci>
                <ci> S </ci>
                <ci> t2 </ci>
                <ci> R </ci>
                <ci> b </ci>
                <ci> N </ci>
                <ci> Ninf </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction fast="false" id="resistant_cell_growth" metaid="COPASI14" name="resistant cell growth" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI14">
              <bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/sbo/SBO:0000393"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/go/GO:0000828"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI14">
                <dcterms:created>
                  <rdf:Description>
                    <dcterms:W3CDTF>2019-08-02T14:36:26Z</dcterms:W3CDTF>
                  </rdf:Description>
                </dcterms:created>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:go:GO:000828"/>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:sbo:SBO:0000393"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfProducts>
          <speciesReference constant="true" species="R" stoichiometry="1"/>
        </listOfProducts>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> tme </ci>
              <apply>
                <ci> growth </ci>
                <ci> b </ci>
                <ci> N </ci>
                <ci> Ninf </ci>
                <ci> R </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
    </listOfReactions>
  </model>
</sbml>