| Autor: |
Brasó-Maristany, Fara, Griguolo, Gaia, Pascual, Tomás, Paré, Laia, Nuciforo, Paolo, Llombart-Cussac, Antonio, Bermejo, Begoña, Oliveira, Mafalda, Morales, Serafín, Martínez, Noelia, Vidal, Maria, Adamo, Barbara, Martínez, Olga, Pernas, Sonia, López, Rafael, Muñoz, Montserrat, Chic, Núria, Galván, Patricia, Garau, Isabel, Manso, Luis |
| Předmět: |
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| Zdroj: |
Nature Communications; 1/20/2020, Vol. 11 Issue 1, p1-11, 11p |
| Abstrakt: |
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 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. HER2-enriched breast cancers within the HER2-positive subtype are addicted to the HER2 pathway. Here, the authors analyse gene expression before, during, and after treatment with anti-HER2-based therapies in the phase II PAMELA clinical trial, finding phenotypic changes induced by treatment. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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