Acquired RAS or EGFR mutations and duration of response to EGFR blockade in colorectal cancer

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  • dc.contributor.author Van Emburgh, Beth O.ca
  • dc.contributor.author Vidal Barrull, Joanaca
  • dc.contributor.author Bellosillo Paricio, Beatrizca
  • dc.contributor.author Albanell Mestres, Joanca
  • dc.contributor.author Montagut Viladot, Claraca
  • dc.contributor.author Bardelli, Albertoca
  • dc.date.accessioned 2018-01-31T08:17:28Z
  • dc.date.available 2018-01-31T08:17:28Z
  • dc.date.issued 2016
  • dc.description.abstract Blockade of the epidermal growth factor receptor (EGFR) with the monoclonal antibodies cetuximab or panitumumab is effective in a subset of colorectal cancers (CRCs), but the emergence of resistance limits the efficacy of these therapeutic agents. At relapse, the majority of patients develop RAS mutations, while a subset acquires EGFR extracellular domain (ECD) mutations. Here we find that patients who experience greater and longer responses to EGFR blockade preferentially develop EGFR ECD mutations, while RAS mutations emerge more frequently in patients with smaller tumour shrinkage and shorter progression-free survival. In circulating cell-free tumour DNA of patients treated with anti-EGFR antibodies, RAS mutations emerge earlier than EGFR ECD variants. Subclonal RAS but not EGFR ECD mutations are present in CRC samples obtained before exposure to EGFR blockade. These data indicate that clonal evolution of drug-resistant cells is associated with the clinical outcome of CRC patients treated with anti-EGFR antibodies
  • dc.description.sponsorship This study was supported by European Community’s Seventh Framework Programme under grant agreement no. 602901 MErCuRIC (A.B. and F.D.N.); European Community’s Seventh Framework Programme under grant agreement no. 635342-2 MoTriColor (A.B. and S.S.); TRANSCAN-2 JTC 2014 contract no. TRS-2015-00000060 INTRACOLOR (S.A.); IMI contract no. 115749 CANCER-ID (A.B.); AIRC 2010 Special Program Molecular Clinical Oncology 5 per mille, Project no. 9970 Extension program (A.B. and S.S.); Fondazione Piemontese per la Ricerca sul Cancro-ONLUS 5 per mille 2011 Ministero della Salute (A.B.); AIRC IG no. 16788 (A.B.); AIRC and the EU under a Marie Curie COFUND (G.G.); Fondo per la Ricerca Locale (ex 60%), Universita` di Torino, 2014 (F.D.N.); Instituto de Salud Carlos III, organismo adscrito al Ministerio de Economía y Competitividad and ‘Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa’ grants PI15/00457 and DTS15/00048 (C.M.); PIE15/00008 and PI15/00146 (J.A.); RETIC Cancer–Instituto de Salud Carlos III RD12/0036/0051 (C.M. and J.A.); 2014SGR740 (J.A.); and Xarxa de Banc de Tumors de Catalunya and Fundació Cellex (C.M.). Investigators at Niguarda Cancer Centers are supported by the grants Terapia Molecolare dei Tumori (A.S.-B. and S.S.) and Dynamic of Tumor Evolution & Therapy (A.S.-B.) from Fondazione Oncologia Niguarda Onlus.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Van Emburgh BO, Arena S, Siravegna G, Lazzari L, Crisafulli G, Corti G. et al. Acquired RAS or EGFR mutations and duration of response to EGFR blockade in colorectal cancer. Nat Commun. 2016 Dec 8;7:13665. DOI: 10.1038/ncomms13665
  • dc.identifier.doi http://dx.doi.org/10.1038/ncomms13665
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/33782
  • dc.language.iso eng
  • dc.publisher Nature Publishing Groupca
  • dc.relation.ispartof Nature Communications. 2016 Dec 8;7:13665
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/602901
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/635342-2
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115749
  • dc.rights Copyright © 2016, The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.other Còlon -- Càncer
  • dc.title Acquired RAS or EGFR mutations and duration of response to EGFR blockade in colorectal cancerca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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