HER-targeted tyrosine kinase inhibitors enhance response to trastuzumab and pertuzumab in HER2-positive breast cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-07-30

AUTHORS

Alexandra Canonici, Laura Ivers, Neil T. Conlon, Kasper Pedersen, Nicola Gaynor, Brigid C. Browne, Neil A. O’Brien, Giuseppe Gullo, Denis M. Collins, Norma O’Donovan, John Crown

ABSTRACT

Despite trastuzumab and pertuzumab improving outcome for patients with HER2-positive metastatic breast cancer, the disease remains fatal for the majority of patients. This study evaluated the anti-proliferative effects of adding anti-HER2 tyrosine kinase inhibitors (TKIs) to trastuzumab and pertuzumab in HER2-positive breast cancer cells. Afatinib was tested alone and in combination with trastuzumab in HER2-positive breast cancer cell lines. TKIs (lapatinib, neratinib, afatinib) combined with trastuzumab and/or pertuzumab were tested in 3 cell lines, with/without amphiregulin and heregulin-1β. Seven of 11 HER2-positive cell lines tested were sensitive to afatinib (IC50 < 80 nM). Afatinib plus trastuzumab produced synergistic growth inhibition in eight cell lines. In trastuzumab-sensitive SKBR3 cells, the TKIs enhanced response to trastuzumab. Pertuzumab alone did not inhibit growth and did not enhance trastuzumab-induced growth inhibition or antibody-dependent cellular cytotoxicity. Pertuzumab enhanced response to trastuzumab when combined with lapatinib but not neratinib or afatinib. In two trastuzumab-resistant cell lines, the TKIs inhibited growth but adding trastuzumab and/or pertuzumab did not improve response compared to TKIs alone. Amphiregulin plus heregulin-1β stimulated proliferation of SKBR3 and MDA-MB-453 cells. In the presence of the growth factors, neither antibody inhibited growth and the TKIs showed significantly reduced activity. The triple combination of trastuzumab, pertuzumab and a TKI showed the strongest anti-proliferative activity in all three cell lines, in the presence of exogenous growth factors. In summary, addition of anti-HER2 TKIs to combined anti-HER2 monoclonal antibody therapy results in enhanced anticancer activity. These data contribute to the rationale for studying maximum HER2 blockade in the clinic. More... »

PAGES

1-11

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10637-018-0649-y

DOI

http://dx.doi.org/10.1007/s10637-018-0649-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105907377

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30062574


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"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Dublin City University", 
          "id": "https://www.grid.ac/institutes/grid.15596.3e", 
          "name": [
            "Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Canonici", 
        "givenName": "Alexandra", 
        "id": "sg:person.0703076461.38", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0703076461.38"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dublin City University", 
          "id": "https://www.grid.ac/institutes/grid.15596.3e", 
          "name": [
            "Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ivers", 
        "givenName": "Laura", 
        "id": "sg:person.016475453577.00", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016475453577.00"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dublin City University", 
          "id": "https://www.grid.ac/institutes/grid.15596.3e", 
          "name": [
            "Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Conlon", 
        "givenName": "Neil T.", 
        "id": "sg:person.01257172532.81", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257172532.81"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dublin City University", 
          "id": "https://www.grid.ac/institutes/grid.15596.3e", 
          "name": [
            "Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Pedersen", 
        "givenName": "Kasper", 
        "id": "sg:person.01112617540.17", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01112617540.17"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dublin City University", 
          "id": "https://www.grid.ac/institutes/grid.15596.3e", 
          "name": [
            "Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gaynor", 
        "givenName": "Nicola", 
        "id": "sg:person.016601451176.97", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016601451176.97"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dublin City University", 
          "id": "https://www.grid.ac/institutes/grid.15596.3e", 
          "name": [
            "Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Browne", 
        "givenName": "Brigid C.", 
        "id": "sg:person.0662142540.33", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0662142540.33"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of California Los Angeles", 
          "id": "https://www.grid.ac/institutes/grid.19006.3e", 
          "name": [
            "Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "O\u2019Brien", 
        "givenName": "Neil A.", 
        "id": "sg:person.01044504340.84", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01044504340.84"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Vincent's University Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412751.4", 
          "name": [
            "Department of Medical Oncology, St Vincent\u2019s University Hospital, Dublin, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gullo", 
        "givenName": "Giuseppe", 
        "id": "sg:person.01223342332.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223342332.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dublin City University", 
          "id": "https://www.grid.ac/institutes/grid.15596.3e", 
          "name": [
            "Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Collins", 
        "givenName": "Denis M.", 
        "id": "sg:person.010157376707.59", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010157376707.59"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dublin City University", 
          "id": "https://www.grid.ac/institutes/grid.15596.3e", 
          "name": [
            "Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "O\u2019Donovan", 
        "givenName": "Norma", 
        "id": "sg:person.01035620375.50", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035620375.50"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Vincent's University Hospital", 
          "id": "https://www.grid.ac/institutes/grid.412751.4", 
          "name": [
            "Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland", 
            "Department of Medical Oncology, St Vincent\u2019s University Hospital, Dublin, Ireland"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Crown", 
        "givenName": "John", 
        "id": "sg:person.01060164243.98", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01060164243.98"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1158/1535-7163.mct-09-1171", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000880356"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2014.56.9590", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005404907"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10637-010-9415-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006267870", 
          "https://doi.org/10.1007/s10637-010-9415-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-03-3856", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006401030"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-03-3856", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006401030"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1470-2045(11)70336-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006777850"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-08-1978", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010964690"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00432-015-2012-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016596336", 
          "https://doi.org/10.1007/s00432-015-2012-4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/jpet.112.197756", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017522498"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa064320", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018697395"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s40262-013-0091-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019821429", 
          "https://doi.org/10.1007/s40262-013-0091-4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1470-2045(14)70320-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021198680"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1470-2045(15)00551-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021556818"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10549-009-0502-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029028113", 
          "https://doi.org/10.1007/s10549-009-0502-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10549-009-0502-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029028113", 
          "https://doi.org/10.1007/s10549-009-0502-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10549-009-0502-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029028113", 
          "https://doi.org/10.1007/s10549-009-0502-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-05-1182", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030336226"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/annonc/mdr484", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030384850"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejm200103153441101", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031768583"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1513750", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032963725"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1201317", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036146499", 
          "https://doi.org/10.1038/sj.onc.1201317"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1201317", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036146499", 
          "https://doi.org/10.1038/sj.onc.1201317"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1634/theoncologist.2008-0001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036452696"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.1148", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040930696"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0960-894x(02)01047-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041163033"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0960-894x(02)01047-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041163033"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1413513", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043562849"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm040159c", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044734359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm040159c", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044734359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/bcr3480", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047618553", 
          "https://doi.org/10.1186/bcr3480"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-07-0701", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048062146"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/annonc/mds221", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051128069"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/oncsis.2012.16", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053536812", 
          "https://doi.org/10.1038/oncsis.2012.16"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-08-4597", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053676255"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.sabcs10-p3-14-24", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063219271"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1387/ijdb.113396se", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1067191337"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2014.32.18_suppl.lba4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1083398373"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1703643", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085866538"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-07-30", 
    "datePublishedReg": "2018-07-30", 
    "description": "Despite trastuzumab and pertuzumab improving outcome for patients with HER2-positive metastatic breast cancer, the disease remains fatal for the majority of patients. This study evaluated the anti-proliferative effects of adding anti-HER2 tyrosine kinase inhibitors (TKIs) to trastuzumab and pertuzumab in HER2-positive breast cancer cells. Afatinib was tested alone and in combination with trastuzumab in HER2-positive breast cancer cell lines. TKIs (lapatinib, neratinib, afatinib) combined with trastuzumab and/or pertuzumab were tested in 3 cell lines, with/without amphiregulin and heregulin-1\u03b2. Seven of 11 HER2-positive cell lines tested were sensitive to afatinib (IC50\u2009<\u200980\u00a0nM). Afatinib plus trastuzumab produced synergistic growth inhibition in eight cell lines. In trastuzumab-sensitive SKBR3 cells, the TKIs enhanced response to trastuzumab. Pertuzumab alone did not inhibit growth and did not enhance trastuzumab-induced growth inhibition or antibody-dependent cellular cytotoxicity. Pertuzumab enhanced response to trastuzumab when combined with lapatinib but not neratinib or afatinib. In two trastuzumab-resistant cell lines, the TKIs inhibited growth but adding trastuzumab and/or pertuzumab did not improve response compared to TKIs alone. Amphiregulin plus heregulin-1\u03b2 stimulated proliferation of SKBR3 and MDA-MB-453 cells. In the presence of the growth factors, neither antibody inhibited growth and the TKIs showed significantly reduced activity. The triple combination of trastuzumab, pertuzumab and a TKI showed the strongest anti-proliferative activity in all three cell lines, in the presence of exogenous growth factors. In summary, addition of anti-HER2 TKIs to combined anti-HER2 monoclonal antibody therapy results in enhanced anticancer activity. These data contribute to the rationale for studying maximum HER2 blockade in the clinic.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1007/s10637-018-0649-y", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.3983731", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1094201", 
        "issn": [
          "0167-6997", 
          "1573-0646"
        ], 
        "name": "Investigational New Drugs", 
        "type": "Periodical"
      }
    ], 
    "name": "HER-targeted tyrosine kinase inhibitors enhance response to trastuzumab and pertuzumab in HER2-positive breast cancer", 
    "pagination": "1-11", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "2908cfb5bb7f0dccab23eb77f018f65219ad7144ae0ceb2a05c60937788c3798"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30062574"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "8309330"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s10637-018-0649-y"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1105907377"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s10637-018-0649-y", 
      "https://app.dimensions.ai/details/publication/pub.1105907377"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T15:15", 
    "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_8663_00000604.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1007%2Fs10637-018-0649-y"
  }
]
 

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.10.1007/s10637-018-0649-y'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10637-018-0649-y'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s10637-018-0649-y'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10637-018-0649-y'


 

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

245 TRIPLES      21 PREDICATES      58 URIs      18 LITERALS      7 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s10637-018-0649-y schema:about anzsrc-for:11
2 anzsrc-for:1112
3 schema:author N4b91ca0ef7794636b7fa7d3e2bd94094
4 schema:citation sg:pub.10.1007/s00432-015-2012-4
5 sg:pub.10.1007/s10549-009-0502-2
6 sg:pub.10.1007/s10637-010-9415-5
7 sg:pub.10.1007/s40262-013-0091-4
8 sg:pub.10.1038/oncsis.2012.16
9 sg:pub.10.1038/sj.onc.1201317
10 sg:pub.10.1186/bcr3480
11 https://doi.org/10.1016/s0960-894x(02)01047-8
12 https://doi.org/10.1016/s1470-2045(11)70336-9
13 https://doi.org/10.1016/s1470-2045(14)70320-1
14 https://doi.org/10.1016/s1470-2045(15)00551-3
15 https://doi.org/10.1021/jm040159c
16 https://doi.org/10.1056/nejm200103153441101
17 https://doi.org/10.1056/nejmoa064320
18 https://doi.org/10.1056/nejmoa1413513
19 https://doi.org/10.1056/nejmoa1513750
20 https://doi.org/10.1056/nejmoa1703643
21 https://doi.org/10.1093/annonc/mdr484
22 https://doi.org/10.1093/annonc/mds221
23 https://doi.org/10.1124/jpet.112.197756
24 https://doi.org/10.1158/0008-5472.can-03-3856
25 https://doi.org/10.1158/0008-5472.can-05-1182
26 https://doi.org/10.1158/0008-5472.can-08-4597
27 https://doi.org/10.1158/0008-5472.sabcs10-p3-14-24
28 https://doi.org/10.1158/1078-0432.ccr-07-0701
29 https://doi.org/10.1158/1078-0432.ccr-08-1978
30 https://doi.org/10.1158/1535-7163.mct-09-1171
31 https://doi.org/10.1200/jco.2014.32.18_suppl.lba4
32 https://doi.org/10.1200/jco.2014.56.9590
33 https://doi.org/10.1387/ijdb.113396se
34 https://doi.org/10.1634/theoncologist.2008-0001
35 https://doi.org/10.18632/oncotarget.1148
36 schema:datePublished 2018-07-30
37 schema:datePublishedReg 2018-07-30
38 schema:description Despite trastuzumab and pertuzumab improving outcome for patients with HER2-positive metastatic breast cancer, the disease remains fatal for the majority of patients. This study evaluated the anti-proliferative effects of adding anti-HER2 tyrosine kinase inhibitors (TKIs) to trastuzumab and pertuzumab in HER2-positive breast cancer cells. Afatinib was tested alone and in combination with trastuzumab in HER2-positive breast cancer cell lines. TKIs (lapatinib, neratinib, afatinib) combined with trastuzumab and/or pertuzumab were tested in 3 cell lines, with/without amphiregulin and heregulin-1β. Seven of 11 HER2-positive cell lines tested were sensitive to afatinib (IC<sub>50</sub> &lt; 80 nM). Afatinib plus trastuzumab produced synergistic growth inhibition in eight cell lines. In trastuzumab-sensitive SKBR3 cells, the TKIs enhanced response to trastuzumab. Pertuzumab alone did not inhibit growth and did not enhance trastuzumab-induced growth inhibition or antibody-dependent cellular cytotoxicity. Pertuzumab enhanced response to trastuzumab when combined with lapatinib but not neratinib or afatinib. In two trastuzumab-resistant cell lines, the TKIs inhibited growth but adding trastuzumab and/or pertuzumab did not improve response compared to TKIs alone. Amphiregulin plus heregulin-1β stimulated proliferation of SKBR3 and MDA-MB-453 cells. In the presence of the growth factors, neither antibody inhibited growth and the TKIs showed significantly reduced activity. The triple combination of trastuzumab, pertuzumab and a TKI showed the strongest anti-proliferative activity in all three cell lines, in the presence of exogenous growth factors. In summary, addition of anti-HER2 TKIs to combined anti-HER2 monoclonal antibody therapy results in enhanced anticancer activity. These data contribute to the rationale for studying maximum HER2 blockade in the clinic.
39 schema:genre research_article
40 schema:inLanguage en
41 schema:isAccessibleForFree false
42 schema:isPartOf sg:journal.1094201
43 schema:name HER-targeted tyrosine kinase inhibitors enhance response to trastuzumab and pertuzumab in HER2-positive breast cancer
44 schema:pagination 1-11
45 schema:productId N1110ed3949704911a15cfd97029d4821
46 N650a8c6f3fb14c13b50f9c3751ee3763
47 N7a2e070ed170460cb8dec44a73e30e8e
48 N9a72aa10cd214124a455df90a052a8c6
49 Ndc7610d74d4e41c79177cb5e86287a86
50 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105907377
51 https://doi.org/10.1007/s10637-018-0649-y
52 schema:sdDatePublished 2019-04-10T15:15
53 schema:sdLicense https://scigraph.springernature.com/explorer/license/
54 schema:sdPublisher Ne04b0677f9d2453a90199c7b2bf391ea
55 schema:url https://link.springer.com/10.1007%2Fs10637-018-0649-y
56 sgo:license sg:explorer/license/
57 sgo:sdDataset articles
58 rdf:type schema:ScholarlyArticle
59 N1110ed3949704911a15cfd97029d4821 schema:name readcube_id
60 schema:value 2908cfb5bb7f0dccab23eb77f018f65219ad7144ae0ceb2a05c60937788c3798
61 rdf:type schema:PropertyValue
62 N4b91ca0ef7794636b7fa7d3e2bd94094 rdf:first sg:person.0703076461.38
63 rdf:rest Na1b6ddd8dc4e4a65974058d915765f2e
64 N57282d33775f400ab0ea2eeb7104e519 rdf:first sg:person.01060164243.98
65 rdf:rest rdf:nil
66 N650a8c6f3fb14c13b50f9c3751ee3763 schema:name pubmed_id
67 schema:value 30062574
68 rdf:type schema:PropertyValue
69 N7a2e070ed170460cb8dec44a73e30e8e schema:name doi
70 schema:value 10.1007/s10637-018-0649-y
71 rdf:type schema:PropertyValue
72 N85199c5ea46642aebae14b05eba62f0b rdf:first sg:person.01035620375.50
73 rdf:rest N57282d33775f400ab0ea2eeb7104e519
74 N9171e19704aa41c2aa181013cbb10cba rdf:first sg:person.01112617540.17
75 rdf:rest Nc97a380e54f748c3835d6b886f41c8d8
76 N9a72aa10cd214124a455df90a052a8c6 schema:name nlm_unique_id
77 schema:value 8309330
78 rdf:type schema:PropertyValue
79 Na1b6ddd8dc4e4a65974058d915765f2e rdf:first sg:person.016475453577.00
80 rdf:rest Nae8a17b0d43047c58ce587d8c19b7983
81 Nae8a17b0d43047c58ce587d8c19b7983 rdf:first sg:person.01257172532.81
82 rdf:rest N9171e19704aa41c2aa181013cbb10cba
83 Nc627dd9b6ee7495c9b85e4a88397ac59 rdf:first sg:person.0662142540.33
84 rdf:rest Ncf94e7062f614d3d9b44929406b580b3
85 Nc97a380e54f748c3835d6b886f41c8d8 rdf:first sg:person.016601451176.97
86 rdf:rest Nc627dd9b6ee7495c9b85e4a88397ac59
87 Ncf94e7062f614d3d9b44929406b580b3 rdf:first sg:person.01044504340.84
88 rdf:rest Nf9eaeaf0c4434f2eabe08e271b1ecd07
89 Ndc7610d74d4e41c79177cb5e86287a86 schema:name dimensions_id
90 schema:value pub.1105907377
91 rdf:type schema:PropertyValue
92 Ne04b0677f9d2453a90199c7b2bf391ea schema:name Springer Nature - SN SciGraph project
93 rdf:type schema:Organization
94 Nf9721e2ed9a84cc7b49ecb92eb8afa3b rdf:first sg:person.010157376707.59
95 rdf:rest N85199c5ea46642aebae14b05eba62f0b
96 Nf9eaeaf0c4434f2eabe08e271b1ecd07 rdf:first sg:person.01223342332.02
97 rdf:rest Nf9721e2ed9a84cc7b49ecb92eb8afa3b
98 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
99 schema:name Medical and Health Sciences
100 rdf:type schema:DefinedTerm
101 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
102 schema:name Oncology and Carcinogenesis
103 rdf:type schema:DefinedTerm
104 sg:grant.3983731 http://pending.schema.org/fundedItem sg:pub.10.1007/s10637-018-0649-y
105 rdf:type schema:MonetaryGrant
106 sg:journal.1094201 schema:issn 0167-6997
107 1573-0646
108 schema:name Investigational New Drugs
109 rdf:type schema:Periodical
110 sg:person.010157376707.59 schema:affiliation https://www.grid.ac/institutes/grid.15596.3e
111 schema:familyName Collins
112 schema:givenName Denis M.
113 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010157376707.59
114 rdf:type schema:Person
115 sg:person.01035620375.50 schema:affiliation https://www.grid.ac/institutes/grid.15596.3e
116 schema:familyName O’Donovan
117 schema:givenName Norma
118 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035620375.50
119 rdf:type schema:Person
120 sg:person.01044504340.84 schema:affiliation https://www.grid.ac/institutes/grid.19006.3e
121 schema:familyName O’Brien
122 schema:givenName Neil A.
123 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01044504340.84
124 rdf:type schema:Person
125 sg:person.01060164243.98 schema:affiliation https://www.grid.ac/institutes/grid.412751.4
126 schema:familyName Crown
127 schema:givenName John
128 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01060164243.98
129 rdf:type schema:Person
130 sg:person.01112617540.17 schema:affiliation https://www.grid.ac/institutes/grid.15596.3e
131 schema:familyName Pedersen
132 schema:givenName Kasper
133 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01112617540.17
134 rdf:type schema:Person
135 sg:person.01223342332.02 schema:affiliation https://www.grid.ac/institutes/grid.412751.4
136 schema:familyName Gullo
137 schema:givenName Giuseppe
138 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223342332.02
139 rdf:type schema:Person
140 sg:person.01257172532.81 schema:affiliation https://www.grid.ac/institutes/grid.15596.3e
141 schema:familyName Conlon
142 schema:givenName Neil T.
143 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257172532.81
144 rdf:type schema:Person
145 sg:person.016475453577.00 schema:affiliation https://www.grid.ac/institutes/grid.15596.3e
146 schema:familyName Ivers
147 schema:givenName Laura
148 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016475453577.00
149 rdf:type schema:Person
150 sg:person.016601451176.97 schema:affiliation https://www.grid.ac/institutes/grid.15596.3e
151 schema:familyName Gaynor
152 schema:givenName Nicola
153 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016601451176.97
154 rdf:type schema:Person
155 sg:person.0662142540.33 schema:affiliation https://www.grid.ac/institutes/grid.15596.3e
156 schema:familyName Browne
157 schema:givenName Brigid C.
158 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0662142540.33
159 rdf:type schema:Person
160 sg:person.0703076461.38 schema:affiliation https://www.grid.ac/institutes/grid.15596.3e
161 schema:familyName Canonici
162 schema:givenName Alexandra
163 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0703076461.38
164 rdf:type schema:Person
165 sg:pub.10.1007/s00432-015-2012-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016596336
166 https://doi.org/10.1007/s00432-015-2012-4
167 rdf:type schema:CreativeWork
168 sg:pub.10.1007/s10549-009-0502-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029028113
169 https://doi.org/10.1007/s10549-009-0502-2
170 rdf:type schema:CreativeWork
171 sg:pub.10.1007/s10637-010-9415-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006267870
172 https://doi.org/10.1007/s10637-010-9415-5
173 rdf:type schema:CreativeWork
174 sg:pub.10.1007/s40262-013-0091-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019821429
175 https://doi.org/10.1007/s40262-013-0091-4
176 rdf:type schema:CreativeWork
177 sg:pub.10.1038/oncsis.2012.16 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053536812
178 https://doi.org/10.1038/oncsis.2012.16
179 rdf:type schema:CreativeWork
180 sg:pub.10.1038/sj.onc.1201317 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036146499
181 https://doi.org/10.1038/sj.onc.1201317
182 rdf:type schema:CreativeWork
183 sg:pub.10.1186/bcr3480 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047618553
184 https://doi.org/10.1186/bcr3480
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1016/s0960-894x(02)01047-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041163033
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1016/s1470-2045(11)70336-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006777850
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1016/s1470-2045(14)70320-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021198680
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1016/s1470-2045(15)00551-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021556818
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1021/jm040159c schema:sameAs https://app.dimensions.ai/details/publication/pub.1044734359
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1056/nejm200103153441101 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031768583
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1056/nejmoa064320 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018697395
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1056/nejmoa1413513 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043562849
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1056/nejmoa1513750 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032963725
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1056/nejmoa1703643 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085866538
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1093/annonc/mdr484 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030384850
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1093/annonc/mds221 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051128069
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1124/jpet.112.197756 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017522498
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1158/0008-5472.can-03-3856 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006401030
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1158/0008-5472.can-05-1182 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030336226
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1158/0008-5472.can-08-4597 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053676255
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1158/0008-5472.sabcs10-p3-14-24 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063219271
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1158/1078-0432.ccr-07-0701 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048062146
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1158/1078-0432.ccr-08-1978 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010964690
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1158/1535-7163.mct-09-1171 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000880356
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1200/jco.2014.32.18_suppl.lba4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083398373
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1200/jco.2014.56.9590 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005404907
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1387/ijdb.113396se schema:sameAs https://app.dimensions.ai/details/publication/pub.1067191337
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1634/theoncologist.2008-0001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036452696
233 rdf:type schema:CreativeWork
234 https://doi.org/10.18632/oncotarget.1148 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040930696
235 rdf:type schema:CreativeWork
236 https://www.grid.ac/institutes/grid.15596.3e schema:alternateName Dublin City University
237 schema:name Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
238 rdf:type schema:Organization
239 https://www.grid.ac/institutes/grid.19006.3e schema:alternateName University of California Los Angeles
240 schema:name Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
241 rdf:type schema:Organization
242 https://www.grid.ac/institutes/grid.412751.4 schema:alternateName St. Vincent's University Hospital
243 schema:name Department of Medical Oncology, St Vincent’s University Hospital, Dublin, Ireland
244 Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
245 rdf:type schema:Organization
 




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


...