dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | ADAM-ARTIGUES, ANNA |
dc.contributor.author | Brasó-Maristany, Fara |
dc.contributor.author | Cervera Vidal, Raimundo |
dc.contributor.author | Tormo, Eduardo |
dc.contributor.author | Arribas López, Joaquin Vicente |
dc.contributor.author | Arenas Lahuerta, Enrique Javier |
dc.contributor.author | Martínez-Sabadell, Alex |
dc.date.accessioned | 2022-09-09T07:25:07Z |
dc.date.available | 2022-09-09T07:25:07Z |
dc.date.issued | 2022-05-20 |
dc.identifier.citation | Adam-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.issn | 2375-2548 |
dc.identifier.uri | https://hdl.handle.net/11351/8085 |
dc.description | Breast cancer; Heterodimerization |
dc.description.abstract | Anti-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.iso | eng |
dc.publisher | American Association for the Advancement of Science |
dc.relation.ispartofseries | Science Advances;8(20) |
dc.rights | Attribution-NonCommercial 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ |
dc.source | Scientia |
dc.subject | Mama - Càncer - Tractament |
dc.subject | Resistència als medicaments |
dc.subject.mesh | Breast Neoplasms |
dc.subject.mesh | /drug therapy |
dc.subject.mesh | Drug Resistance, Neoplasm |
dc.title | Targeting HER2-AXL heterodimerization to overcome resistance to HER2 blockade in breast cancer |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1126/sciadv.abk2746 |
dc.subject.decs | neoplasias de la mama |
dc.subject.decs | /farmacoterapia |
dc.subject.decs | resistencia a los antineoplásicos |
dc.relation.publishversion | http://dx.doi.org/10.1126/sciadv.abk2746 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut 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.pmid | 35594351 |
dc.identifier.wos | 000798164800004 |
dc.relation.projectid | info:eu-repo/grantAgreement/ES/PE2017-2020/FI20%2F00188 |
dc.relation.projectid | info:eu-repo/grantAgreement/ES/PE2013-2016/CB16%2F12%2F00449 |
dc.relation.projectid | info:eu-repo/grantAgreement/ES/PE2017-2020/PI19%2F01181 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |