The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-06

AUTHORS

Luis A. Diaz, Richard T. Williams, Jian Wu, Isaac Kinde, J. Randolph Hecht, Jordan Berlin, Benjamin Allen, Ivana Bozic, Johannes G. Reiter, Martin A. Nowak, Kenneth W. Kinzler, Kelly S. Oliner, Bert Vogelstein

ABSTRACT

Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6 months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion. More... »

PAGES

537

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature11219

DOI

http://dx.doi.org/10.1038/nature11219

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004846070

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22722843


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antibodies, Monoclonal", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Colorectal Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA, Neoplasm", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Drug Resistance, Neoplasm", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Evolution, Molecular", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genes, ras", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mutation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proto-Oncogene Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Proto-Oncogene Proteins p21(ras)", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptor, Epidermal Growth Factor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Selection, Genetic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Time Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "ras Proteins", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Johns Hopkins University", 
          "id": "https://www.grid.ac/institutes/grid.21107.35", 
          "name": [
            "Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21287, USA", 
            "Swim Across America Laboratory at Johns Hopkins, Baltimore, Maryland 21287, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Diaz", 
        "givenName": "Luis A.", 
        "id": "sg:person.0644256174.44", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0644256174.44"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Amgen (United States)", 
          "id": "https://www.grid.ac/institutes/grid.417886.4", 
          "name": [
            "Amgen Inc., Thousand Oaks, California 91320, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Williams", 
        "givenName": "Richard T.", 
        "id": "sg:person.01330372502.69", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01330372502.69"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fourth Military Medical University", 
          "id": "https://www.grid.ac/institutes/grid.233520.5", 
          "name": [
            "Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21287, USA", 
            "State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi\u2019an 710032, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wu", 
        "givenName": "Jian", 
        "id": "sg:person.014003505217.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014003505217.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Johns Hopkins University", 
          "id": "https://www.grid.ac/institutes/grid.21107.35", 
          "name": [
            "Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21287, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kinde", 
        "givenName": "Isaac", 
        "id": "sg:person.01023460537.67", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01023460537.67"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hecht", 
        "givenName": "J. Randolph", 
        "id": "sg:person.01021445032.82", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021445032.82"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Vanderbilt University Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.412807.8", 
          "name": [
            "Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Berlin", 
        "givenName": "Jordan", 
        "id": "sg:person.0631616313.46", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631616313.46"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Harvard University", 
          "id": "https://www.grid.ac/institutes/grid.38142.3c", 
          "name": [
            "Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Allen", 
        "givenName": "Benjamin", 
        "id": "sg:person.01370364137.47", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01370364137.47"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Harvard University", 
          "id": "https://www.grid.ac/institutes/grid.38142.3c", 
          "name": [
            "Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Bozic", 
        "givenName": "Ivana", 
        "id": "sg:person.01066027314.25", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01066027314.25"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Science and Technology Austria", 
          "id": "https://www.grid.ac/institutes/grid.33565.36", 
          "name": [
            "Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA", 
            "IST Austria (Institute of Science and Technology Austria), Klosterneuburg 3400, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Reiter", 
        "givenName": "Johannes G.", 
        "id": "sg:person.01125714710.96", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125714710.96"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Harvard University", 
          "id": "https://www.grid.ac/institutes/grid.38142.3c", 
          "name": [
            "Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Nowak", 
        "givenName": "Martin A.", 
        "id": "sg:person.01161070716.44", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01161070716.44"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Johns Hopkins University", 
          "id": "https://www.grid.ac/institutes/grid.21107.35", 
          "name": [
            "Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21287, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kinzler", 
        "givenName": "Kenneth W.", 
        "id": "sg:person.0620642630.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0620642630.54"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Amgen (United States)", 
          "id": "https://www.grid.ac/institutes/grid.417886.4", 
          "name": [
            "Amgen Inc., Thousand Oaks, California 91320, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Oliner", 
        "givenName": "Kelly S.", 
        "id": "sg:person.0641611202.61", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0641611202.61"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Johns Hopkins University", 
          "id": "https://www.grid.ac/institutes/grid.21107.35", 
          "name": [
            "Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21287, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Vogelstein", 
        "givenName": "Bert", 
        "id": "sg:person.011173760757.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011173760757.54"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-09-2017", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000663841"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1534/genetics.105.049791", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004941016"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1534/genetics.105.049791", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004941016"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature09627", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005907434", 
          "https://doi.org/10.1038/nature09627"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm.2609", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007295122", 
          "https://doi.org/10.1038/nm.2609"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1007726107", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011196174"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-07-0589", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011526716"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.mbs.2005.07.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017474227"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0712345105", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018833150"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1141478", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023671304"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-07-0605", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023944589"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pmed.0020017", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023971579"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa0804385", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025462530"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmeth898", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028618204", 
          "https://doi.org/10.1038/nmeth898"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nmeth898", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028618204", 
          "https://doi.org/10.1038/nmeth898"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0507904102", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030122941"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0808319105", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030741698"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0501870102", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031178420"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2007.14.7116", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031599680"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ccr.2009.11.022", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033302817"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa0800668", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034531394"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.tpb.2009.10.008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034651071"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3324/haematol.2009.015271", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035903073"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/scitranslmed.3002543", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042185166"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jnci/djp240", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044933543"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm.1789", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051933380", 
          "https://doi.org/10.1038/nm.1789"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0027682", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052576018"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/scisignal.2001148", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062682223"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/scitranslmed.3002442", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062687072"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1077357078", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2012-06", 
    "datePublishedReg": "2012-06-01", 
    "description": "Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6 months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/nature11219", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2440141", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2519328", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2469185", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2634365", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2427472", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.6189093", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2440181", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2634325", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2479546", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2515827", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2471197", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2469166", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.3789560", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1018957", 
        "issn": [
          "0090-0028", 
          "1476-4687"
        ], 
        "name": "Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "7404", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "486"
      }
    ], 
    "name": "The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers", 
    "pagination": "537", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "1717d42f2466df904dd80fdc93cd1b4e72eb3ede59fc0628471cc486676f99b3"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "22722843"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "0410462"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/nature11219"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1004846070"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/nature11219", 
      "https://app.dimensions.ai/details/publication/pub.1004846070"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T17:20", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8672_00000435.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/nature11219"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature11219'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature11219'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature11219'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature11219'


 

This table displays all metadata directly associated to this object as RDF triples.

343 TRIPLES      21 PREDICATES      71 URIs      35 LITERALS      23 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/nature11219 schema:about N02303207187048188354922c04e43242
2 N1535485d58244f29bc93d41ba3efd85f
3 N53ea4eaecf24447da4a2b971938bd808
4 N61e8dd08c19c4c109311f4f4310fab29
5 N733140a3e46047e6a46dce3dd68c92f9
6 N80ad76f2f7fc4d7fae54a4d56c9da197
7 N80b99b93653544d18a35424a646e72cf
8 N8c7ce0a1960642dd94064c8816fed0ed
9 N9d83368f1aac4d15968f46529fe3acf4
10 Na16357ad94bb42f388b64acb74d426d5
11 Na5d06baa5bd942d78d8a0f527cc78387
12 Nae7e0a1c7a5849838ced7695e147a177
13 Ncacd4868085645708e9c24863cffbbfb
14 Nf894bc26a098491ebc99ae9f4016d2ea
15 anzsrc-for:11
16 anzsrc-for:1112
17 schema:author N426c1448bc1140b7b52bae0f5dd45b10
18 schema:citation sg:pub.10.1038/nature09627
19 sg:pub.10.1038/nm.1789
20 sg:pub.10.1038/nm.2609
21 sg:pub.10.1038/nmeth898
22 https://app.dimensions.ai/details/publication/pub.1077357078
23 https://doi.org/10.1016/j.ccr.2009.11.022
24 https://doi.org/10.1016/j.mbs.2005.07.003
25 https://doi.org/10.1016/j.tpb.2009.10.008
26 https://doi.org/10.1056/nejmoa0800668
27 https://doi.org/10.1056/nejmoa0804385
28 https://doi.org/10.1073/pnas.0501870102
29 https://doi.org/10.1073/pnas.0507904102
30 https://doi.org/10.1073/pnas.0712345105
31 https://doi.org/10.1073/pnas.0808319105
32 https://doi.org/10.1073/pnas.1007726107
33 https://doi.org/10.1093/jnci/djp240
34 https://doi.org/10.1126/science.1141478
35 https://doi.org/10.1126/scisignal.2001148
36 https://doi.org/10.1126/scitranslmed.3002442
37 https://doi.org/10.1126/scitranslmed.3002543
38 https://doi.org/10.1158/0008-5472.can-07-0589
39 https://doi.org/10.1158/0008-5472.can-07-0605
40 https://doi.org/10.1158/1078-0432.ccr-09-2017
41 https://doi.org/10.1200/jco.2007.14.7116
42 https://doi.org/10.1371/journal.pmed.0020017
43 https://doi.org/10.1371/journal.pone.0027682
44 https://doi.org/10.1534/genetics.105.049791
45 https://doi.org/10.3324/haematol.2009.015271
46 schema:datePublished 2012-06
47 schema:datePublishedReg 2012-06-01
48 schema:description Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6 months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.
49 schema:genre research_article
50 schema:inLanguage en
51 schema:isAccessibleForFree true
52 schema:isPartOf N2fdaccaa15e64480856d645ff3ba8bd8
53 N7efcb5edd8d84543b141dd6d5a7fc043
54 sg:journal.1018957
55 schema:name The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers
56 schema:pagination 537
57 schema:productId N0850b9c5253f419cb5c2914f5d2b4888
58 N9f490e63c1d04bf5bded85a8e043a13a
59 Nacf66da4cc494ddd909c0fa265c0ad03
60 Nc27db795ffb64880aeb895ce039fc5c2
61 Nc58b911a76834013aba7dea5ea55c2ea
62 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004846070
63 https://doi.org/10.1038/nature11219
64 schema:sdDatePublished 2019-04-10T17:20
65 schema:sdLicense https://scigraph.springernature.com/explorer/license/
66 schema:sdPublisher N414776b082294a0cb3b1c348352983e0
67 schema:url https://www.nature.com/articles/nature11219
68 sgo:license sg:explorer/license/
69 sgo:sdDataset articles
70 rdf:type schema:ScholarlyArticle
71 N02303207187048188354922c04e43242 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
72 schema:name Proto-Oncogene Proteins
73 rdf:type schema:DefinedTerm
74 N0850b9c5253f419cb5c2914f5d2b4888 schema:name readcube_id
75 schema:value 1717d42f2466df904dd80fdc93cd1b4e72eb3ede59fc0628471cc486676f99b3
76 rdf:type schema:PropertyValue
77 N1535485d58244f29bc93d41ba3efd85f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
78 schema:name Mutation
79 rdf:type schema:DefinedTerm
80 N2fdaccaa15e64480856d645ff3ba8bd8 schema:volumeNumber 486
81 rdf:type schema:PublicationVolume
82 N372c77e90ef445dfbf085c04dcf4cca6 rdf:first sg:person.01161070716.44
83 rdf:rest N5a0c0ba50ed44a3fab9567fb872dff0e
84 N414776b082294a0cb3b1c348352983e0 schema:name Springer Nature - SN SciGraph project
85 rdf:type schema:Organization
86 N426c1448bc1140b7b52bae0f5dd45b10 rdf:first sg:person.0644256174.44
87 rdf:rest Nb9d0abe07b994d18a07d7ea77b3f343f
88 N53ea4eaecf24447da4a2b971938bd808 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
89 schema:name Genes, ras
90 rdf:type schema:DefinedTerm
91 N591cea0133e247c88280089491f66199 rdf:first sg:person.0641611202.61
92 rdf:rest N8eac26fbc54543af9930d4b404aa97bf
93 N59dbcf234bd042e6be1e5323f8ed3df3 rdf:first sg:person.01021445032.82
94 rdf:rest N64e91ade4e6c4b5282a8d22c1ca34f86
95 N5a0c0ba50ed44a3fab9567fb872dff0e rdf:first sg:person.0620642630.54
96 rdf:rest N591cea0133e247c88280089491f66199
97 N61e8dd08c19c4c109311f4f4310fab29 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
98 schema:name Receptor, Epidermal Growth Factor
99 rdf:type schema:DefinedTerm
100 N625f292bec08455c842a8036e65f6f11 rdf:first sg:person.01066027314.25
101 rdf:rest Neb740f00f729419898911f5e199e2ed8
102 N64e91ade4e6c4b5282a8d22c1ca34f86 rdf:first sg:person.0631616313.46
103 rdf:rest N74a0ef3609a94d6ca9fd28ac54476bed
104 N733140a3e46047e6a46dce3dd68c92f9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
105 schema:name Humans
106 rdf:type schema:DefinedTerm
107 N74a0ef3609a94d6ca9fd28ac54476bed rdf:first sg:person.01370364137.47
108 rdf:rest N625f292bec08455c842a8036e65f6f11
109 N7efcb5edd8d84543b141dd6d5a7fc043 schema:issueNumber 7404
110 rdf:type schema:PublicationIssue
111 N80ad76f2f7fc4d7fae54a4d56c9da197 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
112 schema:name Colorectal Neoplasms
113 rdf:type schema:DefinedTerm
114 N80b99b93653544d18a35424a646e72cf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
115 schema:name Time Factors
116 rdf:type schema:DefinedTerm
117 N8c7ce0a1960642dd94064c8816fed0ed schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
118 schema:name DNA, Neoplasm
119 rdf:type schema:DefinedTerm
120 N8eac26fbc54543af9930d4b404aa97bf rdf:first sg:person.011173760757.54
121 rdf:rest rdf:nil
122 N9d83368f1aac4d15968f46529fe3acf4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
123 schema:name Proto-Oncogene Proteins p21(ras)
124 rdf:type schema:DefinedTerm
125 N9f490e63c1d04bf5bded85a8e043a13a schema:name pubmed_id
126 schema:value 22722843
127 rdf:type schema:PropertyValue
128 Na16357ad94bb42f388b64acb74d426d5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
129 schema:name Evolution, Molecular
130 rdf:type schema:DefinedTerm
131 Na5d06baa5bd942d78d8a0f527cc78387 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
132 schema:name ras Proteins
133 rdf:type schema:DefinedTerm
134 Na8bf6965ee83412889f0ba3dfceb0966 rdf:first sg:person.014003505217.43
135 rdf:rest Nebf95ab6bdc94864a5a83be9cce37e83
136 Nacf66da4cc494ddd909c0fa265c0ad03 schema:name doi
137 schema:value 10.1038/nature11219
138 rdf:type schema:PropertyValue
139 Nae7e0a1c7a5849838ced7695e147a177 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name Antibodies, Monoclonal
141 rdf:type schema:DefinedTerm
142 Nb9d0abe07b994d18a07d7ea77b3f343f rdf:first sg:person.01330372502.69
143 rdf:rest Na8bf6965ee83412889f0ba3dfceb0966
144 Nc27db795ffb64880aeb895ce039fc5c2 schema:name dimensions_id
145 schema:value pub.1004846070
146 rdf:type schema:PropertyValue
147 Nc58b911a76834013aba7dea5ea55c2ea schema:name nlm_unique_id
148 schema:value 0410462
149 rdf:type schema:PropertyValue
150 Ncacd4868085645708e9c24863cffbbfb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
151 schema:name Selection, Genetic
152 rdf:type schema:DefinedTerm
153 Neb740f00f729419898911f5e199e2ed8 rdf:first sg:person.01125714710.96
154 rdf:rest N372c77e90ef445dfbf085c04dcf4cca6
155 Nebf95ab6bdc94864a5a83be9cce37e83 rdf:first sg:person.01023460537.67
156 rdf:rest N59dbcf234bd042e6be1e5323f8ed3df3
157 Nf894bc26a098491ebc99ae9f4016d2ea schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
158 schema:name Drug Resistance, Neoplasm
159 rdf:type schema:DefinedTerm
160 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
161 schema:name Medical and Health Sciences
162 rdf:type schema:DefinedTerm
163 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
164 schema:name Oncology and Carcinogenesis
165 rdf:type schema:DefinedTerm
166 sg:grant.2427472 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
167 rdf:type schema:MonetaryGrant
168 sg:grant.2440141 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
169 rdf:type schema:MonetaryGrant
170 sg:grant.2440181 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
171 rdf:type schema:MonetaryGrant
172 sg:grant.2469166 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
173 rdf:type schema:MonetaryGrant
174 sg:grant.2469185 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
175 rdf:type schema:MonetaryGrant
176 sg:grant.2471197 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
177 rdf:type schema:MonetaryGrant
178 sg:grant.2479546 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
179 rdf:type schema:MonetaryGrant
180 sg:grant.2515827 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
181 rdf:type schema:MonetaryGrant
182 sg:grant.2519328 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
183 rdf:type schema:MonetaryGrant
184 sg:grant.2634325 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
185 rdf:type schema:MonetaryGrant
186 sg:grant.2634365 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
187 rdf:type schema:MonetaryGrant
188 sg:grant.3789560 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
189 rdf:type schema:MonetaryGrant
190 sg:grant.6189093 http://pending.schema.org/fundedItem sg:pub.10.1038/nature11219
191 rdf:type schema:MonetaryGrant
192 sg:journal.1018957 schema:issn 0090-0028
193 1476-4687
194 schema:name Nature
195 rdf:type schema:Periodical
196 sg:person.01021445032.82 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
197 schema:familyName Hecht
198 schema:givenName J. Randolph
199 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01021445032.82
200 rdf:type schema:Person
201 sg:person.01023460537.67 schema:affiliation https://www.grid.ac/institutes/grid.21107.35
202 schema:familyName Kinde
203 schema:givenName Isaac
204 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01023460537.67
205 rdf:type schema:Person
206 sg:person.01066027314.25 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
207 schema:familyName Bozic
208 schema:givenName Ivana
209 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01066027314.25
210 rdf:type schema:Person
211 sg:person.011173760757.54 schema:affiliation https://www.grid.ac/institutes/grid.21107.35
212 schema:familyName Vogelstein
213 schema:givenName Bert
214 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011173760757.54
215 rdf:type schema:Person
216 sg:person.01125714710.96 schema:affiliation https://www.grid.ac/institutes/grid.33565.36
217 schema:familyName Reiter
218 schema:givenName Johannes G.
219 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125714710.96
220 rdf:type schema:Person
221 sg:person.01161070716.44 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
222 schema:familyName Nowak
223 schema:givenName Martin A.
224 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01161070716.44
225 rdf:type schema:Person
226 sg:person.01330372502.69 schema:affiliation https://www.grid.ac/institutes/grid.417886.4
227 schema:familyName Williams
228 schema:givenName Richard T.
229 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01330372502.69
230 rdf:type schema:Person
231 sg:person.01370364137.47 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
232 schema:familyName Allen
233 schema:givenName Benjamin
234 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01370364137.47
235 rdf:type schema:Person
236 sg:person.014003505217.43 schema:affiliation https://www.grid.ac/institutes/grid.233520.5
237 schema:familyName Wu
238 schema:givenName Jian
239 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014003505217.43
240 rdf:type schema:Person
241 sg:person.0620642630.54 schema:affiliation https://www.grid.ac/institutes/grid.21107.35
242 schema:familyName Kinzler
243 schema:givenName Kenneth W.
244 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0620642630.54
245 rdf:type schema:Person
246 sg:person.0631616313.46 schema:affiliation https://www.grid.ac/institutes/grid.412807.8
247 schema:familyName Berlin
248 schema:givenName Jordan
249 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631616313.46
250 rdf:type schema:Person
251 sg:person.0641611202.61 schema:affiliation https://www.grid.ac/institutes/grid.417886.4
252 schema:familyName Oliner
253 schema:givenName Kelly S.
254 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0641611202.61
255 rdf:type schema:Person
256 sg:person.0644256174.44 schema:affiliation https://www.grid.ac/institutes/grid.21107.35
257 schema:familyName Diaz
258 schema:givenName Luis A.
259 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0644256174.44
260 rdf:type schema:Person
261 sg:pub.10.1038/nature09627 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005907434
262 https://doi.org/10.1038/nature09627
263 rdf:type schema:CreativeWork
264 sg:pub.10.1038/nm.1789 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051933380
265 https://doi.org/10.1038/nm.1789
266 rdf:type schema:CreativeWork
267 sg:pub.10.1038/nm.2609 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007295122
268 https://doi.org/10.1038/nm.2609
269 rdf:type schema:CreativeWork
270 sg:pub.10.1038/nmeth898 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028618204
271 https://doi.org/10.1038/nmeth898
272 rdf:type schema:CreativeWork
273 https://app.dimensions.ai/details/publication/pub.1077357078 schema:CreativeWork
274 https://doi.org/10.1016/j.ccr.2009.11.022 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033302817
275 rdf:type schema:CreativeWork
276 https://doi.org/10.1016/j.mbs.2005.07.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017474227
277 rdf:type schema:CreativeWork
278 https://doi.org/10.1016/j.tpb.2009.10.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034651071
279 rdf:type schema:CreativeWork
280 https://doi.org/10.1056/nejmoa0800668 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034531394
281 rdf:type schema:CreativeWork
282 https://doi.org/10.1056/nejmoa0804385 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025462530
283 rdf:type schema:CreativeWork
284 https://doi.org/10.1073/pnas.0501870102 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031178420
285 rdf:type schema:CreativeWork
286 https://doi.org/10.1073/pnas.0507904102 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030122941
287 rdf:type schema:CreativeWork
288 https://doi.org/10.1073/pnas.0712345105 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018833150
289 rdf:type schema:CreativeWork
290 https://doi.org/10.1073/pnas.0808319105 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030741698
291 rdf:type schema:CreativeWork
292 https://doi.org/10.1073/pnas.1007726107 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011196174
293 rdf:type schema:CreativeWork
294 https://doi.org/10.1093/jnci/djp240 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044933543
295 rdf:type schema:CreativeWork
296 https://doi.org/10.1126/science.1141478 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023671304
297 rdf:type schema:CreativeWork
298 https://doi.org/10.1126/scisignal.2001148 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062682223
299 rdf:type schema:CreativeWork
300 https://doi.org/10.1126/scitranslmed.3002442 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062687072
301 rdf:type schema:CreativeWork
302 https://doi.org/10.1126/scitranslmed.3002543 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042185166
303 rdf:type schema:CreativeWork
304 https://doi.org/10.1158/0008-5472.can-07-0589 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011526716
305 rdf:type schema:CreativeWork
306 https://doi.org/10.1158/0008-5472.can-07-0605 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023944589
307 rdf:type schema:CreativeWork
308 https://doi.org/10.1158/1078-0432.ccr-09-2017 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000663841
309 rdf:type schema:CreativeWork
310 https://doi.org/10.1200/jco.2007.14.7116 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031599680
311 rdf:type schema:CreativeWork
312 https://doi.org/10.1371/journal.pmed.0020017 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023971579
313 rdf:type schema:CreativeWork
314 https://doi.org/10.1371/journal.pone.0027682 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052576018
315 rdf:type schema:CreativeWork
316 https://doi.org/10.1534/genetics.105.049791 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004941016
317 rdf:type schema:CreativeWork
318 https://doi.org/10.3324/haematol.2009.015271 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035903073
319 rdf:type schema:CreativeWork
320 https://www.grid.ac/institutes/grid.19006.3e schema:alternateName University of California Los Angeles
321 schema:name Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
322 rdf:type schema:Organization
323 https://www.grid.ac/institutes/grid.21107.35 schema:alternateName Johns Hopkins University
324 schema:name Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21287, USA
325 Swim Across America Laboratory at Johns Hopkins, Baltimore, Maryland 21287, USA
326 rdf:type schema:Organization
327 https://www.grid.ac/institutes/grid.233520.5 schema:alternateName Fourth Military Medical University
328 schema:name Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21287, USA
329 State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical University, Xi’an 710032, China
330 rdf:type schema:Organization
331 https://www.grid.ac/institutes/grid.33565.36 schema:alternateName Institute of Science and Technology Austria
332 schema:name IST Austria (Institute of Science and Technology Austria), Klosterneuburg 3400, Austria
333 Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA
334 rdf:type schema:Organization
335 https://www.grid.ac/institutes/grid.38142.3c schema:alternateName Harvard University
336 schema:name Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA
337 rdf:type schema:Organization
338 https://www.grid.ac/institutes/grid.412807.8 schema:alternateName Vanderbilt University Medical Center
339 schema:name Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
340 rdf:type schema:Organization
341 https://www.grid.ac/institutes/grid.417886.4 schema:alternateName Amgen (United States)
342 schema:name Amgen Inc., Thousand Oaks, California 91320, USA
343 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...