Pharmacological induction of chromatin remodeling drives chemosensitization in triple-negative breast cancer.
Cell Rep Med
; 5(4): 101504, 2024 Apr 16.
Article
en En
| MEDLINE
| ID: mdl-38593809
ABSTRACT
Targeted therapies have improved outcomes for certain cancer subtypes, but cytotoxic chemotherapy remains a mainstay for triple-negative breast cancer (TNBC). The epithelial-to-mesenchymal transition (EMT) is a developmental program co-opted by cancer cells that promotes metastasis and chemoresistance. There are no therapeutic strategies specifically targeting mesenchymal-like cancer cells. We report that the US Food and Drug Administration (FDA)-approved chemotherapeutic eribulin induces ZEB1-SWI/SNF-directed chromatin remodeling to reverse EMT that curtails the metastatic propensity of TNBC preclinical models. Eribulin induces mesenchymal-to-epithelial transition (MET) in primary TNBC in patients, but conventional chemotherapy does not. In the treatment-naive setting, but not after acquired resistance to other agents, eribulin sensitizes TNBC cells to subsequent treatment with other chemotherapeutics. These findings provide an epigenetic mechanism of action of eribulin, supporting its use early in the disease process for MET induction to prevent metastatic progression and chemoresistance. These findings warrant prospective clinical evaluation of the chemosensitizing effects of eribulin in the treatment-naive setting.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama Triple Negativas
/
Furanos
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Policétidos Poliéteres
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Cetonas
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Antineoplásicos
Límite:
Humans
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Cell Rep Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos