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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/173290
Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade
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The HER2-enriched (HER2-E) subtype within HER2-positive (HER2+) breast cancer is highly addicted to the HER2 pathway. However, ∼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 trastu- zumab 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.
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BRASÓ MARISTANY, Fara, GRIGUOLO, Gaia, PASCUAL, Tomás, PARÉ, Laia, NUCIFORO, Paolo, LLOMBART CUSSAC, Antonio, BERMEJO DE LAS HERAS, Begoña, OLIVEIRA, Mafalda, MORALES, Serafín, MARTÍNEZ, Noelia, VIDAL LOSADA, Maria jesús, ADAMO, Barbara, MARTÍNEZ SÁEZ, Olga, PERNAS, Sònia, LÓPEZ, Rafael, MUÑOZ MATEU, Montserrat, CHIC RUCHÉ, Núria, GALVÁN, Patricia, GARAU, Isabel, MANSO, Luis, ALARCÓN, Jesús, MARTÍNEZ, Eduardo, GREGORIO JORDÁN, Sara, GOMIS I CABRÉ, Roger, VILLAGRASA, Patricia, CORTÉS, Javier, CIRUELOS, Eva, PRAT APARICIO, Aleix. Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade. _Nature Communications_. 2020. Vol. 11. [consulta: 8 de abril de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/173290]