Collateral resistance to taxanes in enzalutamide-resistant prostate cancer through aberrant androgen receptor and its variants.
Cancer Sci
; 109(10): 3224-3234, 2018 Oct.
Article
em En
| MEDLINE
| ID: mdl-30051622
ABSTRACT
Currently, the optimal sequential use of androgen receptor (AR) axis-targeted agents and taxane chemotherapies remains undetermined. We aimed to elucidate the resistance status between taxanes and enzalutamide, and the functional role of the AR axis. Enzalutamide-resistant 22Rv1 cells showed collateral resistance to taxanes, including docetaxel and cabazitaxel. However, taxane-resistant cells showed no collateral resistance to enzalutamide; taxane-resistant cells expressed comparable protein levels of full-length AR and AR variants. Knockdown of both full-length AR and AR variants rendered cells sensitive to taxanes, whereas knockdown of AR variants sensitized cells to enzalutamide, but not to taxanes. In contrast, overexpression of full-length AR rendered cells resistant to taxanes. Consistently, the prostate-specific antigen response and progression-free survival in docetaxel chemotherapy were worse in cases with prior use of ARAT agents compared with cases without. Collateral resistance to taxanes was evident after obtaining enzalutamide resistance, and aberrant AR signaling might be involved in taxane resistance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Receptores Androgênicos
/
Resistencia a Medicamentos Antineoplásicos
/
Taxoides
/
Neoplasias de Próstata Resistentes à Castração
Limite:
Aged
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão