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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorAdam-Artigues, Anna
dc.contributor.authorArenas Lahuerta, Enrique Javier
dc.contributor.authorMartínez-Sabadell, Alex
dc.contributor.authorBrasó-Maristany, Fara
dc.contributor.authorCervera Vidal, Raimundo
dc.contributor.authorTormo, Eduardo
dc.contributor.authorArribas López, Joaquin Vicente
dc.date.accessioned2022-09-09T07:25:07Z
dc.date.available2022-09-09T07:25:07Z
dc.date.issued2022-05-20
dc.identifier.citationAdam-Artigues A, Arenas EJ, Martínez-Sabadell A, Brasó-Maristany F, Cervera R, Tormo E, et al. Targeting HER2-AXL heterodimerization to overcome resistance to HER2 blockade in breast cancer. Sci Adv. 2022 May 20;8(20):eabk2746.
dc.identifier.issn2375-2548
dc.identifier.urihttp://hdl.handle.net/11351/8085
dc.descriptionBreast cancer; Heterodimerization
dc.description.abstractAnti-HER2 therapies have markedly improved prognosis of HER2-positive breast cancer. However, different mechanisms play a role in treatment resistance. Here, we identified AXL overexpression as an essential mechanism of trastuzumab resistance. AXL orchestrates epithelial-to-mesenchymal transition and heterodimerizes with HER2, leading to activation of PI3K/AKT and MAPK pathways in a ligand-independent manner. Genetic depletion and pharmacological inhibition of AXL restored trastuzumab response in vitro and in vivo. AXL inhibitor plus trastuzumab achieved complete regression in trastuzumab-resistant patient-derived xenograft models. Moreover, AXL expression in HER2-positive primary tumors was able to predict prognosis. Data from the PAMELA trial showed a change in AXL expression during neoadjuvant dual HER2 blockade, supporting its role in resistance. Therefore, our study highlights the importance of targeting AXL in combination with anti-HER2 drugs across HER2-amplified breast cancer patients with high AXL expression. Furthermore, it unveils the potential value of AXL as a druggable prognostic biomarker in HER2-positive breast cancer.
dc.language.isoeng
dc.publisherAmerican Association for the Advancement of Science
dc.relation.ispartofseriesScience Advances;8(20)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectMama - Càncer - Tractament
dc.subjectResistència als medicaments
dc.subject.meshBreast Neoplasms
dc.subject.mesh/drug therapy
dc.subject.meshDrug Resistance, Neoplasm
dc.titleTargeting HER2-AXL heterodimerization to overcome resistance to HER2 blockade in breast cancer
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1126/sciadv.abk2746
dc.subject.decsneoplasias de la mama
dc.subject.decs/farmacoterapia
dc.subject.decsresistencia a los antineoplásicos
dc.relation.publishversionhttp://dx.doi.org/10.1126/sciadv.abk2746
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Adam-Artigues A, Cervera R] INCLIVA Biomedical Research Institute, Valencia, Spain. [Arenas EJ] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Center for Biomedical Network Research on Cancer (CIBERONC), Madrid, Spain. [Martínez-Sabadell A] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Brasó-Maristany F] August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. Department of Medical Oncology, Hospital Clinic de Barcelona, Barcelona, Spain. [Tormo E] INCLIVA Biomedical Research Institute, Valencia, Spain. Center for Biomedical Network Research on Cancer (CIBERONC), Madrid, Spain. [Arribas J] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Center for Biomedical Network Research on Cancer (CIBERONC), Madrid, Spain. Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
dc.identifier.pmid35594351
dc.identifier.wos000798164800004
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2017-2020/FI20%2F00188
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/CB16%2F12%2F00449
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2017-2020/PI19%2F01181
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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