Computational analysis of image-based drug profiling predicts synergistic drug combinations: applications in triple-negative breast cancer.
Identifieur interne : 003155 ( PubMed/Curation ); précédent : 003154; suivant : 003156Computational analysis of image-based drug profiling predicts synergistic drug combinations: applications in triple-negative breast cancer.
Auteurs : Miriam B. Brandl [États-Unis] ; Eddy Pasquier [France] ; Fuhai Li [États-Unis] ; Dominik Beck [Australie] ; Sufang Zhang [États-Unis] ; Hong Zhao [États-Unis] ; Maria Kavallaris [Australie] ; Stephen T C. Wong [États-Unis]Source :
- Molecular oncology [ 1878-0261 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Apoptose (), Benzamides (usage thérapeutique), Femelle, Humains, Kinésine (antagonistes et inhibiteurs), Kinésine (métabolisme), Lignée cellulaire tumorale, Mitose (), Pyrimidines (usage thérapeutique), Quinazolines (usage thérapeutique), Souris, Souris de lignée BALB C, Synergie des médicaments, Tests d'activité antitumorale sur modèle de xénogreffe, Thiones (usage thérapeutique), Tumeurs du sein triple-négatives (métabolisme), Tumeurs du sein triple-négatives (traitement médicamenteux), Vinblastine (usage thérapeutique).
- MESH :
- antagonistes et inhibiteurs : Kinésine.
- métabolisme : Kinésine, Tumeurs du sein triple-négatives.
- traitement médicamenteux : Tumeurs du sein triple-négatives.
- usage thérapeutique : Benzamides, Pyrimidines, Quinazolines, Thiones, Vinblastine.
- Animaux, Apoptose, Femelle, Humains, Lignée cellulaire tumorale, Mitose, Souris, Souris de lignée BALB C, Synergie des médicaments, Tests d'activité antitumorale sur modèle de xénogreffe.
English descriptors
- KwdEn :
- Animals, Apoptosis (drug effects), Benzamides (therapeutic use), Cell Line, Tumor, Drug Synergism, Female, Humans, Kinesin (antagonists & inhibitors), Kinesin (metabolism), Mice, Mice, Inbred BALB C, Mitosis (drug effects), Pyrimidines (therapeutic use), Quinazolines (therapeutic use), Thiones (therapeutic use), Triple Negative Breast Neoplasms (drug therapy), Triple Negative Breast Neoplasms (metabolism), Vinblastine (therapeutic use), Xenograft Model Antitumor Assays.
- MESH :
- chemical , antagonists & inhibitors : Kinesin.
- chemical , metabolism : Kinesin.
- chemical , therapeutic use : Benzamides, Pyrimidines, Quinazolines, Thiones, Vinblastine.
- drug effects : Apoptosis, Mitosis.
- drug therapy : Triple Negative Breast Neoplasms.
- metabolism : Triple Negative Breast Neoplasms.
- Animals, Cell Line, Tumor, Drug Synergism, Female, Humans, Mice, Mice, Inbred BALB C, Xenograft Model Antitumor Assays.
Abstract
An imaged-based profiling and analysis system was developed to predict clinically effective synergistic drug combinations that could accelerate the identification of effective multi-drug therapies for the treatment of triple-negative breast cancer and other challenging malignancies. The identification of effective drug combinations for the treatment of triple-negative breast cancer (TNBC) was achieved by integrating high-content screening, computational analysis, and experimental biology. The approach was based on altered cellular phenotypes induced by 55 FDA-approved drugs and biologically active compounds, acquired using fluorescence microscopy and retained in multivariate compound profiles. Dissimilarities between compound profiles guided the identification of 5 combinations, which were assessed for qualitative interaction on TNBC cell growth. The combination of the microtubule-targeting drug vinblastine with KSP/Eg5 motor protein inhibitors monastrol or ispinesib showed potent synergism in 3 independent TNBC cell lines, which was not substantiated in normal fibroblasts. The synergistic interaction was mediated by an increase in mitotic arrest with cells demonstrating typical ispinesib-induced monopolar mitotic spindles, which translated into enhanced apoptosis induction. The antitumour activity of the combination vinblastine/ispinesib was confirmed in an orthotopic mouse model of TNBC. Compared to single drug treatment, combination treatment significantly reduced tumour growth without causing increased toxicity. Image-based profiling and analysis led to the rapid discovery of a drug combination effective against TNBC in vitro and in vivo, and has the potential to lead to the development of new therapeutic options in other hard-to-treat cancers.
DOI: 10.1016/j.molonc.2014.06.007
PubMed: 24997502
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Brandl</name><affiliation wicri:level="1"><nlm:affiliation>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; School of Engineering and Information Technology, University of New South Wales, Canberra, ACT, 2600, Australia; Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; School of Engineering and Information Technology, University of New South Wales, Canberra, ACT, 2600, Australia; Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030</wicri:regionArea></affiliation></author><author><name sortKey="Pasquier, Eddy" sort="Pasquier, Eddy" uniqKey="Pasquier E" first="Eddy" last="Pasquier">Eddy Pasquier</name><affiliation wicri:level="1"><nlm:affiliation>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; Metronomics Global Health Initiative, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; Metronomics Global Health Initiative, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Li, Fuhai" sort="Li, Fuhai" uniqKey="Li F" first="Fuhai" last="Li">Fuhai Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030</wicri:regionArea></affiliation></author><author><name sortKey="Beck, Dominik" sort="Beck, Dominik" uniqKey="Beck D" first="Dominik" last="Beck">Dominik Beck</name><affiliation wicri:level="1"><nlm:affiliation>Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Sufang" sort="Zhang, Sufang" uniqKey="Zhang S" first="Sufang" last="Zhang">Sufang Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030</wicri:regionArea></affiliation></author><author><name sortKey="Zhao, Hong" sort="Zhao, Hong" uniqKey="Zhao H" first="Hong" last="Zhao">Hong Zhao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA. 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Wong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24997502</idno><idno type="pmid">24997502</idno><idno type="doi">10.1016/j.molonc.2014.06.007</idno><idno type="wicri:Area/PubMed/Corpus">003265</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003265</idno><idno type="wicri:Area/PubMed/Curation">003155</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">003155</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Computational analysis of image-based drug profiling predicts synergistic drug combinations: applications in triple-negative breast cancer.</title><author><name sortKey="Brandl, Miriam B" sort="Brandl, Miriam B" uniqKey="Brandl M" first="Miriam B" last="Brandl">Miriam B. Brandl</name><affiliation wicri:level="1"><nlm:affiliation>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; School of Engineering and Information Technology, University of New South Wales, Canberra, ACT, 2600, Australia; Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; School of Engineering and Information Technology, University of New South Wales, Canberra, ACT, 2600, Australia; Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030</wicri:regionArea></affiliation></author><author><name sortKey="Pasquier, Eddy" sort="Pasquier, Eddy" uniqKey="Pasquier E" first="Eddy" last="Pasquier">Eddy Pasquier</name><affiliation wicri:level="1"><nlm:affiliation>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; Metronomics Global Health Initiative, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; Metronomics Global Health Initiative, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Li, Fuhai" sort="Li, Fuhai" uniqKey="Li F" first="Fuhai" last="Li">Fuhai Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030</wicri:regionArea></affiliation></author><author><name sortKey="Beck, Dominik" sort="Beck, Dominik" uniqKey="Beck D" first="Dominik" last="Beck">Dominik Beck</name><affiliation wicri:level="1"><nlm:affiliation>Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Sufang" sort="Zhang, Sufang" uniqKey="Zhang S" first="Sufang" last="Zhang">Sufang Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030</wicri:regionArea></affiliation></author><author><name sortKey="Zhao, Hong" sort="Zhao, Hong" uniqKey="Zhao H" first="Hong" last="Zhao">Hong Zhao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA. Electronic address: hzhao@houstonmethodist.org.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030</wicri:regionArea></affiliation></author><author><name sortKey="Kavallaris, Maria" sort="Kavallaris, Maria" uniqKey="Kavallaris M" first="Maria" last="Kavallaris">Maria Kavallaris</name><affiliation wicri:level="1"><nlm:affiliation>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, University of New South Wales, NSW, 2052, Australia. Electronic address: m.kavallaris@ccia.unsw.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, University of New South Wales, NSW, 2052</wicri:regionArea></affiliation></author><author><name sortKey="Wong, Stephen T C" sort="Wong, Stephen T C" uniqKey="Wong S" first="Stephen T C" last="Wong">Stephen T C. Wong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030</wicri:regionArea></affiliation></author></analytic><series><title level="j">Molecular oncology</title><idno type="eISSN">1878-0261</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Apoptosis (drug effects)</term><term>Benzamides (therapeutic use)</term><term>Cell Line, Tumor</term><term>Drug Synergism</term><term>Female</term><term>Humans</term><term>Kinesin (antagonists & inhibitors)</term><term>Kinesin (metabolism)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mitosis (drug effects)</term><term>Pyrimidines (therapeutic use)</term><term>Quinazolines (therapeutic use)</term><term>Thiones (therapeutic use)</term><term>Triple Negative Breast Neoplasms (drug therapy)</term><term>Triple Negative Breast Neoplasms (metabolism)</term><term>Vinblastine (therapeutic use)</term><term>Xenograft Model Antitumor Assays</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Apoptose ()</term><term>Benzamides (usage thérapeutique)</term><term>Femelle</term><term>Humains</term><term>Kinésine (antagonistes et inhibiteurs)</term><term>Kinésine (métabolisme)</term><term>Lignée cellulaire tumorale</term><term>Mitose ()</term><term>Pyrimidines (usage thérapeutique)</term><term>Quinazolines (usage thérapeutique)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Synergie des médicaments</term><term>Tests d'activité antitumorale sur modèle de xénogreffe</term><term>Thiones (usage thérapeutique)</term><term>Tumeurs du sein triple-négatives (métabolisme)</term><term>Tumeurs du sein triple-négatives (traitement médicamenteux)</term><term>Vinblastine (usage thérapeutique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Kinesin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Kinesin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Benzamides</term><term>Pyrimidines</term><term>Quinazolines</term><term>Thiones</term><term>Vinblastine</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Kinésine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Mitosis</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Triple Negative Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Triple Negative Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Kinésine</term><term>Tumeurs du sein triple-négatives</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs du sein triple-négatives</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Benzamides</term><term>Pyrimidines</term><term>Quinazolines</term><term>Thiones</term><term>Vinblastine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Drug Synergism</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Xenograft Model Antitumor Assays</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Apoptose</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Mitose</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Synergie des médicaments</term><term>Tests d'activité antitumorale sur modèle de xénogreffe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">An imaged-based profiling and analysis system was developed to predict clinically effective synergistic drug combinations that could accelerate the identification of effective multi-drug therapies for the treatment of triple-negative breast cancer and other challenging malignancies. The identification of effective drug combinations for the treatment of triple-negative breast cancer (TNBC) was achieved by integrating high-content screening, computational analysis, and experimental biology. The approach was based on altered cellular phenotypes induced by 55 FDA-approved drugs and biologically active compounds, acquired using fluorescence microscopy and retained in multivariate compound profiles. Dissimilarities between compound profiles guided the identification of 5 combinations, which were assessed for qualitative interaction on TNBC cell growth. The combination of the microtubule-targeting drug vinblastine with KSP/Eg5 motor protein inhibitors monastrol or ispinesib showed potent synergism in 3 independent TNBC cell lines, which was not substantiated in normal fibroblasts. The synergistic interaction was mediated by an increase in mitotic arrest with cells demonstrating typical ispinesib-induced monopolar mitotic spindles, which translated into enhanced apoptosis induction. The antitumour activity of the combination vinblastine/ispinesib was confirmed in an orthotopic mouse model of TNBC. Compared to single drug treatment, combination treatment significantly reduced tumour growth without causing increased toxicity. Image-based profiling and analysis led to the rapid discovery of a drug combination effective against TNBC in vitro and in vivo, and has the potential to lead to the development of new therapeutic options in other hard-to-treat cancers.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24997502</PMID><DateCreated><Year>2014</Year><Month>12</Month><Day>03</Day></DateCreated><DateCompleted><Year>2015</Year><Month>08</Month><Day>19</Day></DateCompleted><DateRevised><Year>2017</Year><Month>11</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1878-0261</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><Issue>8</Issue><PubDate><Year>2014</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Molecular oncology</Title><ISOAbbreviation>Mol Oncol</ISOAbbreviation></Journal><ArticleTitle>Computational analysis of image-based drug profiling predicts synergistic drug combinations: applications in triple-negative breast cancer.</ArticleTitle><Pagination><MedlinePgn>1548-60</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.molonc.2014.06.007</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1574-7891(14)00131-8</ELocationID><Abstract><AbstractText>An imaged-based profiling and analysis system was developed to predict clinically effective synergistic drug combinations that could accelerate the identification of effective multi-drug therapies for the treatment of triple-negative breast cancer and other challenging malignancies. The identification of effective drug combinations for the treatment of triple-negative breast cancer (TNBC) was achieved by integrating high-content screening, computational analysis, and experimental biology. The approach was based on altered cellular phenotypes induced by 55 FDA-approved drugs and biologically active compounds, acquired using fluorescence microscopy and retained in multivariate compound profiles. Dissimilarities between compound profiles guided the identification of 5 combinations, which were assessed for qualitative interaction on TNBC cell growth. The combination of the microtubule-targeting drug vinblastine with KSP/Eg5 motor protein inhibitors monastrol or ispinesib showed potent synergism in 3 independent TNBC cell lines, which was not substantiated in normal fibroblasts. The synergistic interaction was mediated by an increase in mitotic arrest with cells demonstrating typical ispinesib-induced monopolar mitotic spindles, which translated into enhanced apoptosis induction. The antitumour activity of the combination vinblastine/ispinesib was confirmed in an orthotopic mouse model of TNBC. Compared to single drug treatment, combination treatment significantly reduced tumour growth without causing increased toxicity. Image-based profiling and analysis led to the rapid discovery of a drug combination effective against TNBC in vitro and in vivo, and has the potential to lead to the development of new therapeutic options in other hard-to-treat cancers.</AbstractText><CopyrightInformation>Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Brandl</LastName><ForeName>Miriam B</ForeName><Initials>MB</Initials><AffiliationInfo><Affiliation>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; School of Engineering and Information Technology, University of New South Wales, Canberra, ACT, 2600, Australia; Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pasquier</LastName><ForeName>Eddy</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; Metronomics Global Health Initiative, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Fuhai</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beck</LastName><ForeName>Dominik</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Sufang</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Hong</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA. Electronic address: hzhao@houstonmethodist.org.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kavallaris</LastName><ForeName>Maria</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, University of New South Wales, NSW, 2052, Australia. Electronic address: m.kavallaris@ccia.unsw.edu.au.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wong</LastName><ForeName>Stephen T C</ForeName><Initials>ST</Initials><AffiliationInfo><Affiliation>Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College of Cornell University, Houston, TX, 77030, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 CA121225</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>K99 CA149169</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R00 CA149169</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U54CA149169</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U54 CA149196</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>06</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mol Oncol</MedlineTA><NlmUniqueID>101308230</NlmUniqueID><ISSNLinking>1574-7891</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001549">Benzamides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C470243">KIF11 protein, 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