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  • IGF2 is an actionable target that identifies a distinct subpopulation of colorectal cancer patients with marginal response to anti-EGFR therapies | Science Translational Medicine
    this site Jessica Erriquez Cancer Genetics Candiolo Cancer Institute FPO IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Claudio Isella Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Oncogenomics Candiolo Cancer Institute FPO IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Paolo M Comoglio Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Molecular Clinical Oncology Candiolo Cancer Institute FPO IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Enzo Medico Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Oncogenomics Candiolo Cancer Institute FPO IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sabine Tejpar University Hospital Gasthuisberg 3000 Leuven Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site Eva Budinská Institute of Biostatistics and Analyses Masaryk University 611 37 Brno Czech Republic Regional Center of Applied Molecular Oncology Masaryk Memorial Cancer Institute 656 53 Brno Czech Republic Find this author on Google Scholar Find this author on PubMed Search for this author on this site Livio Trusolino Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Translational Cancer Medicine Candiolo Cancer Institute Fondazione del Piemonte per l Oncologia FPO Istituto di Ricovero e Cura a Carattere Scientifico IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Andrea Bertotti Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Translational Cancer Medicine Candiolo Cancer Institute Fondazione del Piemonte per l Oncologia FPO Istituto di Ricovero e Cura a Carattere Scientifico IRCCS 10060 Candiolo Torino Italy National Institute of Biostructures and Biosystems 00136 Rome Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Article Figures Data Info Metrics eLetters PDF Submit a Response to This Article Compose eLetter Title Contents More information about text formats Plain text Plain text No HTML tags allowed Web page addresses and e mail addresses turn into links automatically Lines and paragraphs break automatically Upload Tables and Figures Attach tables e g doc and figures jpg gif tif by choosing the desired file and then uploading them below Add a new file Upload Files must be less than 100 MB Allowed file types doc jpg jpeg gif tif pdf File names can only contain the following characters A Z a z 0 9 Author Information Contributors First name and middle name First or given name e g Peter Last Name Your last or family name e g MacMoody Email Your email address e g higgs boson gmail com

    Original URL path: http://stm.sciencemag.org/content/7/272/272ra12.e-letters (2016-02-10)
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  • IGF2 is an actionable target that identifies a distinct subpopulation of colorectal cancer patients with marginal response to anti-EGFR therapies | Science Translational Medicine
    site Barbara Lupo Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Translational Cancer Medicine Candiolo Cancer Institute Fondazione del Piemonte per l Oncologia FPO Istituto di Ricovero e Cura a Carattere Scientifico IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jessica Erriquez Cancer Genetics Candiolo Cancer Institute FPO IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Claudio Isella Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Oncogenomics Candiolo Cancer Institute FPO IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Paolo M Comoglio Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Molecular Clinical Oncology Candiolo Cancer Institute FPO IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Enzo Medico Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Oncogenomics Candiolo Cancer Institute FPO IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sabine Tejpar University Hospital Gasthuisberg 3000 Leuven Belgium Find this author on Google Scholar Find this author on PubMed Search for this author on this site Eva Budinská Institute of Biostatistics and Analyses Masaryk University 611 37 Brno Czech Republic Regional Center of Applied Molecular Oncology Masaryk Memorial Cancer Institute 656 53 Brno Czech Republic Find this author on Google Scholar Find this author on PubMed Search for this author on this site Livio Trusolino Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Translational Cancer Medicine Candiolo Cancer Institute Fondazione del Piemonte per l Oncologia FPO Istituto di Ricovero e Cura a Carattere Scientifico IRCCS 10060 Candiolo Torino Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Andrea Bertotti Department of Oncology University of Torino Medical School 10060 Candiolo Torino Italy Translational Cancer Medicine Candiolo Cancer Institute Fondazione del Piemonte per l Oncologia FPO Istituto di Ricovero e Cura a Carattere Scientifico IRCCS 10060 Candiolo Torino Italy National Institute of Biostructures and Biosystems 00136 Rome Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Article Figures Data Info Metrics eLetters PDF Log in to view full text As a service to the community AAAS Science has made this article free with registration Username Enter your Sciencemag org username Password Enter the password that accompanies your username Forgot your username or password Log in Register for Free Join Subscribe Recommend a subscription to your library Help for librarians Science Translational Medicine Vol 7 Issue 272 28 January 2015 Table of Contents Article Tools Email Thank you for your

    Original URL path: http://stm.sciencemag.org/content/7/272/272ra12.full (2016-02-10)
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  • Table of Contents — January 28, 2015, 7 (272) | Science Translational Medicine
    Summary Abstract Full Text PDF IGF2 is an actionable target that identifies a distinct subpopulation of colorectal cancer patients with marginal response to anti EGFR therapies By Eugenia R Zanella Francesco Galimi Francesco Sassi Giorgia Migliardi Francesca Cottino Simonetta M Leto Barbara Lupo Jessica Erriquez Claudio Isella Paolo M Comoglio Enzo Medico Sabine Tejpar Eva Budinská Livio Trusolino Andrea Bertotti Science Translational Medicine 28 Jan 2015 272ra12 Colorectal cancers that display reduced sensitivity to EGFR inhibition and strong IGF2 overexpression can be effectively treated by dual EGFR IGF2 blockade Editor s Summary Abstract Full Text PDF Editors Choice TRIPOD puts prediction models on a firmer footing By Chester L Drum Science Translational Medicine 28 Jan 2015 272ec14 International standards for clinical prediction models should improve the quality of reporting Full Text Therapeutic treasure hunt in the myeloid secretome By Ebru Erbay Science Translational Medicine 28 Jan 2015 272ec15 Myeloid derived growth factor infusion might be superior to and safer than bone marrow cell transfusion in treating myocardial infarction Full Text MYCing progress against immunosuppression associated cancers By David E Gerber Science Translational Medicine 28 Jan 2015 272ec16 Molecular profiling provides insights into HIV related lymphoma pathogenesis Full Text SORTing out lipid handling in atherosclerosis By Elvin Price Science Translational Medicine 28 Jan 2015 272ec17 Sortilin mediates LDL uptake into macrophages which contributes to foam cell formation and atherogenesis Full Text Just keep breathing How mitochondrial metabolism influences sepsis outcome By Henrique Serezani Science Translational Medicine 28 Jan 2015 272ec18 UCP2 inhibition of fatty acid metabolism controls inflammasome activation and animal survival during polymicrobial sepsis Full Text Breaking up is bad for the heart By Nathan J White Science Translational Medicine 28 Jan 2015 272ec19 Inhibition of dynamin related protein 1 prevents cardiac mitochondria from splitting prevents organ damage and improves

    Original URL path: http://stm.sciencemag.org/content/7/272 (2016-02-10)
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  • Table of Contents — January 28, 2015, 7 (272) | Science Translational Medicine
    s Summary Abstract Full Text PDF IGF2 is an actionable target that identifies a distinct subpopulation of colorectal cancer patients with marginal response to anti EGFR therapies By Eugenia R Zanella Francesco Galimi Francesco Sassi Giorgia Migliardi Francesca Cottino Simonetta M Leto Barbara Lupo Jessica Erriquez Claudio Isella Paolo M Comoglio Enzo Medico Sabine Tejpar Eva Budinská Livio Trusolino Andrea Bertotti Science Translational Medicine 28 Jan 2015 272ra12 Colorectal cancers that display reduced sensitivity to EGFR inhibition and strong IGF2 overexpression can be effectively treated by dual EGFR IGF2 blockade Editor s Summary Abstract Full Text PDF Editors Choice TRIPOD puts prediction models on a firmer footing By Chester L Drum Science Translational Medicine 28 Jan 2015 272ec14 International standards for clinical prediction models should improve the quality of reporting Full Text Therapeutic treasure hunt in the myeloid secretome By Ebru Erbay Science Translational Medicine 28 Jan 2015 272ec15 Myeloid derived growth factor infusion might be superior to and safer than bone marrow cell transfusion in treating myocardial infarction Full Text MYCing progress against immunosuppression associated cancers By David E Gerber Science Translational Medicine 28 Jan 2015 272ec16 Molecular profiling provides insights into HIV related lymphoma pathogenesis Full Text SORTing out lipid handling in atherosclerosis By Elvin Price Science Translational Medicine 28 Jan 2015 272ec17 Sortilin mediates LDL uptake into macrophages which contributes to foam cell formation and atherogenesis Full Text Just keep breathing How mitochondrial metabolism influences sepsis outcome By Henrique Serezani Science Translational Medicine 28 Jan 2015 272ec18 UCP2 inhibition of fatty acid metabolism controls inflammasome activation and animal survival during polymicrobial sepsis Full Text Breaking up is bad for the heart By Nathan J White Science Translational Medicine 28 Jan 2015 272ec19 Inhibition of dynamin related protein 1 prevents cardiac mitochondria from splitting prevents organ damage and

    Original URL path: http://stm.sciencemag.org/content/7/272.toc (2016-02-10)
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  • VI 7 IP 272 4099 http stm sciencemag org content 7 272 272ra12 short 4100 http stm sciencemag org content 7 272 272ra12 full AB Among patients with colorectal cancer who benefit from therapy targeted to the epidermal growth factor receptor EGFR stable disease SD occurs more frequently than massive regressions Exploring the mechanisms of this incomplete sensitivity to devise more efficacious treatments will likely improve patients outcomes We tested therapies tailored around hypothesis generating molecular features in patient derived xenografts xenopatients which originated from 125 independent samples that did not harbor established resistance conferring mutations Samples from xenopatients that responded to cetuximab an anti EGFR agent with disease stabilization displayed high levels of EGFR family ligands and receptors indicating high EGFR pathway activity Five of 21 SD models 23 8 characterized by particularly high expression of EGFR and EGFR family members regressed after intensified EGFR blockade by cetuximab and a small molecule inhibitor In addition a subset of cases in which enhanced EGFR inhibition was unproductive 6 of 16 37 5 exhibited marked overexpression of insulin like growth factor 2 IGF2 Enrichment of IGF2 overexpressors among cases with SD was demonstrated in the entire xenopatient collection and was confirmed

    Original URL path: http://stm.sciencemag.org/highwire/citation/196069/medlars (2016-02-10)
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  • Advancement of Science VO 7 IS 272 SP 272ra12 OP 272ra12 DO 10 1126 scitranslmed 3010445 UL http stm sciencemag org content 7 272 272ra12 abstract AB Among patients with colorectal cancer who benefit from therapy targeted to the epidermal growth factor receptor EGFR stable disease SD occurs more frequently than massive regressions Exploring the mechanisms of this incomplete sensitivity to devise more efficacious treatments will likely improve patients outcomes We tested therapies tailored around hypothesis generating molecular features in patient derived xenografts xenopatients which originated from 125 independent samples that did not harbor established resistance conferring mutations Samples from xenopatients that responded to cetuximab an anti EGFR agent with disease stabilization displayed high levels of EGFR family ligands and receptors indicating high EGFR pathway activity Five of 21 SD models 23 8 characterized by particularly high expression of EGFR and EGFR family members regressed after intensified EGFR blockade by cetuximab and a small molecule inhibitor In addition a subset of cases in which enhanced EGFR inhibition was unproductive 6 of 16 37 5 exhibited marked overexpression of insulin like growth factor 2 IGF2 Enrichment of IGF2 overexpressors among cases with SD was demonstrated in the entire xenopatient collection and

    Original URL path: http://stm.sciencemag.org/highwire/citation/196069/refworks (2016-02-10)
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  • EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype | Science Translational Medicine
    this author on PubMed Search for this author on this site Dimitri Vordos AP HP Hôpitaux Universitaires Henri Mondor Service d Urologie 94000 Créteil France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Agnès Laplanche Département de Biostatistique et d Epidémiologie Institut de Cancérologie Gustave Roussy 94805 Villejuif France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Pascale Maillé AP HP Hôpitaux Universitaires Henri Mondor Département de Pathologie 94000 Créteil France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Pascale Soyeux INSERM Unité 955 94000 Créteil France Université Paris Est Faculté de Médecine 94000 Créteil France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Karina Ofualuka INSERM Unité 955 94000 Créteil France Université Paris Est Faculté de Médecine 94000 Créteil France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Fabien Reyal CNRS UMR 144 Institut Curie 75005 Paris France Institut Curie Centre de Recherche 75005 Paris France Institut Curie Département de Chirurgie 75005 Paris France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Anne Biton CNRS UMR 144 Institut Curie 75005 Paris France Institut Curie Centre de Recherche 75005 Paris France INSERM U900 Institut Curie 75005 Paris France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mathilde Sibony AP HP Hôpital Cochin Département de Pathologie 75014 Paris France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xavier Paoletti INSERM U900 Institut Curie 75005 Paris France Service de Biostatistique Institut Curie 75005 Paris France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jennifer Southgate Jack Birch Unit of Molecular Carcinogenesis Department of Biology University of York York Y010 5DD UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Simone Benhamou CNRS UMR 8200 Institut de Cancérologie Gustave Roussy 94805 Villejuif France INSERM U946 75010 Paris France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Thierry Lebret Service d Urologie Hôpital Foch 92150 Suresnes France Université de Versailles Saint Quentin en Yvelines Faculté de Médecine Paris Ile de France Ouest 78280 Guyancourt France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yves Allory AP HP Hôpitaux Universitaires Henri Mondor Département de Pathologie 94000 Créteil France INSERM Unité 955 94000 Créteil France Université Paris Est Faculté de Médecine 94000 Créteil France AP HP Hôpitaux Universitaires Henri Mondor Plateforme de Ressources Biologiques 94000 Créteil France Find this author on Google Scholar Find this author

    Original URL path: http://stm.sciencemag.org/content/6/244/244ra91 (2016-02-10)
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  • Clonal status of actionable driver events and the timing of mutational processes in cancer evolution | Science Translational Medicine
    this author on Google Scholar Find this author on PubMed Search for this author on this site Charles Swanton Cancer Research UK London Research Institute London WC2A 3LY UK UCL Cancer Institute CRUK Lung Cancer Centre of Excellence Paul O Gorman Building Huntley Street London WC1E 6DD UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Article Figures Data Info Metrics eLetters PDF You are currently viewing the abstract View Full Text Username Enter your Sciencemag org username Password Enter the password that accompanies your username Forgot your username or password Log in Join Subscribe Purchase Article Activate Member Account Renew Subscription Recommend a subscription to your library Help for librarians Abstract Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies We analyzed nine cancer types to determine the subclonal frequencies of driver events to time mutational processes during cancer evolution and to identify drivers of subclonal expansions Although mutations in known driver genes typically occurred early in cancer evolution we also identified later subclonal actionable mutations including BRAF V600E IDH1 R132H PIK3CA E545K EGFR L858R and KRAS G12D which may compromise the efficacy of targeted therapy approaches More than 20 of IDH1 mutations in glioblastomas and 15 of mutations in genes in the PI3K phosphatidylinositol 3 kinase AKT mTOR mammalian target of rapamycin signaling axis across all tumor types were subclonal Mutations in the RAS MEK mitogen activated protein kinase kinase signaling axis were less likely to be subclonal than mutations in genes associated with PI3K AKT mTOR signaling Analysis of late mutations revealed a link between APOBEC mediated mutagenesis and the acquisition of subclonal driver mutations and uncovered putative cancer genes involved in subclonal expansions including CTNNA2 and ATXN1 Our results provide a pan cancer census of driver events within the context of intratumor heterogeneity and reveal patterns of tumor evolution across cancers The frequent presence of subclonal driver mutations suggests the need to stratify targeted therapy response according to the proportion of tumor cells in which the driver is identified Copyright 2015 American Association for the Advancement of Science View Full Text Science Translational Medicine Vol 7 Issue 283 15 April 2015 Table of Contents Article Tools Email Thank you for your interest in spreading the word about Science Translational Medicine NOTE We only request your email address so that the person you are recommending the page to knows that you wanted them to see it and that it is not junk mail We do not capture any email address Your Email Your Name Send To Enter multiple addresses on separate lines or separate them with commas You are going to email the following Clonal status of actionable driver events and the timing of mutational processes in cancer evolution Message Subject Your Name has forwarded a page to you from Science Translational Medicine Message Body Your Name thought you

    Original URL path: http://stm.sciencemag.org/content/7/283/283ra54 (2016-02-10)
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