Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade
| Autor: | Noelia Martínez, Paolo Nuciforo, Begoña Bermejo, Laia Paré, Patricia Villagrasa, Serafin Morales, J. Alarcón, Eva Ciruelos, Olga Martínez, Tomás Pascual, Aleix Prat, Montserrat Muñoz, Barbara Adamo, I Garau, Sara Gregorio, Fara Brasó-Maristany, Gaia Griguolo, Javier Cortes, Roger R. Gomis, Nuria Chic, Rafael López, Sonia Pernas, Maria Vidal, Antonio Llombart-Cussac, Mafalda Oliveira, Patricia Galván, Eduardo Martínez, Luis Manso |
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| Přispěvatelé: | Institut Català de la Salut, [Brasó-Maristany F] Department of Medical Oncology, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Carrer del Rosselló, 149-153, 08036 Barcelona, Spain. [Griguolo G] Department of Medical Oncology, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Carrer del Rosselló, 149-153, 08036 Barcelona, Spain. Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35124 Padova, Italy. Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Via Gattamelata, 64, 35128 Padova, Italy. [Pascual T] Department of Medical Oncology, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Carrer del Rosselló, 149-153, 08036 Barcelona, Spain. SOLTI Breast Cancer Research Group, Carrer de Balmes, 115, 08008 Barcelona, Spain. [Paré L] SOLTI Breast Cancer Research Group, Carrer de Balmes, 115, 08008 Barcelona, Spain. [Nuciforo P, Oliveira M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Llombart-Cussac A] Hospital Universitario Arnau de Vilanova, Carrer de Sant Clement, 12, 46015 Valencia, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Receptor ErbB-2 Biopsy Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] humanos resistencia a medicamentos Drug Resistance General Physics and Astronomy Medicaments antineoplàstics - Ús terapèutic neoplasias de la mama Disease Drug resistance supervivencia celular Antineoplastic Agents Immunological 0302 clinical medicine Breast cancer Mama - Càncer Trastuzumab Antineoplastic Combined Chemotherapy Protocols Medicine antineoplásicos Breast Other subheadings::/therapeutic use [Other subheadings] Receptor skin and connective tissue diseases neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] Multidisciplinary resultado del tratamiento protocolos de quimioterapia antineoplásica combinada línea celular adulto Phenotype Neoadjuvant Therapy Fenotip Treatment Outcome Oncology mama 030220 oncology & carcinogenesis Female medicine.drug Adult Cell Survival Science biopsia Antineoplastic Agents Breast Neoplasms Lapatinib Article General Biochemistry Genetics and Molecular Biology Cell Line Càncer de mama 03 medical and health sciences Cell Line Tumor mental disorders Biomarkers Tumor Humans perfiles de expresión génica terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] neoplasms tratamiento neoadyuvante business.industry Otros calificadores::/uso terapéutico [Otros calificadores] Gene Expression Profiling General Chemistry Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] medicine.disease Blockade 030104 developmental biology Drug Resistance Neoplasm Cancer research Gene expression business |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Scientia Nature Communications r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA instname r-FHPC. Repositorio Institucional de Producción Científica de la Fundación del Hospital Provincial de Castellón NATURE COMMUNICATIONS r-FISABIO. Repositorio Institucional de Producción Científica r-FISABIO: Repositorio Institucional de Producción Científica Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020) |
| ISSN: | 2041-1723 |
| Popis: | The HER2-enriched (HER2-E) subtype within HER2-positive (HER2+) breast cancer is highly addicted to the HER2 pathway. However, similar to 20-60% of HER2+/HER2-E tumors do not achieve a complete response following anti-HER2 therapies. Here we evaluate gene expression data before, during and after neoadjuvant treatment with lapatinib and trastuzumab in HER2+/HER2-E tumors of the PAMELA trial and breast cancer cell lines. Our results reveal that dual HER2 blockade in HER2-E disease induces a low-proliferative Luminal A phenotype both in patient's tumors and in vitro models. These biological changes are more evident in hormone receptor-positive (HR+) disease compared to HR-negative disease. Interestingly, increasing the luminal phenotype with anti-HER2 therapy increased sensitivity to CDK4/6 inhibition. Finally, discontinuation of HER2-targeted therapy in vitro, or acquired resistance to anti-HER2 therapy, leads to restoration of the original HER2-E phenotype. Our findings support the use of maintenance anti-HER2 therapy and the therapeutic exploitation of subtype switching with CDK4/6 inhibition. This study was funded by the project P116/00904, integrated in the Plan Estatal I+D+I and co-funded by Instituto de Salud Carlos III -Subdireccion General de Evaluacion and European Regional Development Fund (ERDF) (to A.P.), Pas a Pas (to A.P.), Save the Mama (to A.P.), Breast Cancer Now -2018NOVPCC1294 (to A.P.), and Fundacion Cientifica Asociacion Espanola Contra el Cancer -Ayuda Postdoctoral AECC 2017 (to F. B-M). We are indebted to the Biobank and the Cytometry and cell sorting core facilities of the Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) for their technical help. |
| Databáze: | OpenAIRE |
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