Targeting bromodomain and extraterminal proteins in breast cancer.
Pharmacol Res
; 129: 156-176, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29154989
ABSTRACT
Breast cancer is a collection of distinct tumor subtypes that are driven by unique gene expression profiles. These transcriptomes are controlled by various epigenetic marks that dictate which genes are expressed and suppressed. During carcinogenesis, extensive restructuring of the epigenome occurs, including aberrant acetylation, alteration of methylation patterns, and accumulation of epigenetic readers at oncogenes. As epigenetic alterations are reversible, epigenome-modulating drugs could provide a mechanism to silence numerous oncogenes simultaneously. Here, we review the impact of inhibitors of the Bromodomain and Extraterminal (BET) family of epigenetic readers in breast cancer. These agents, including the prototypical BET inhibitor JQ1, have been shown to suppress a variety of oncogenic pathways while inducing minimal, if any, toxicity in models of several subtypes of breast cancer. BET inhibitors also synergize with multiple approved anti-cancer drugs, providing a greater response in breast cancer cell lines and mouse models than either single agent. The combined findings of the studies discussed here provide an excellent rationale for the continued investigation of the utility of BET inhibitors in breast cancer.
Palavras-chave
ARV-825 PubChem CID 92044400; Anti-cancer drugs; BET inhibitor; BETd-246 PubChem CID 131698640; Breast cancer; Bromodomain and extraterminal protein; Drug synergy; I-BET151 PubChem CID 52912189; I-BET762 PubChem CID 46943432; JQ1 PubChem CID 46907787; MS417 PubChem CID 59190723; OTX015 PubChem CID 9936746; THZ1 PubChem CID 73602827; Transcriptional control; XD14 PubChem CID 52670832; dBET1 PubChem CID 91799313
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Proteínas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article