Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling.
Cancer Cell
; 32(4): 474-489.e6, 2017 10 09.
Article
em En
| MEDLINE
| ID: mdl-29017058
ABSTRACT
Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma (PC) and represents the major therapeutic target for treating metastatic prostate cancer (mPC). Though highly effective, AR antagonism can produce tumors that bypass a functional requirement for AR, often through neuroendocrine (NE) transdifferentiation. Through the molecular assessment of mPCs over two decades, we find a phenotypic shift has occurred in mPC with the emergence of an AR-null NE-null phenotype. These "double-negative" PCs are notable for elevated FGF and MAPK pathway activity, which can bypass AR dependence. Pharmacological inhibitors of MAPK or FGFR repressed the growth of double-negative PCs in vitro and in vivo. Our results indicate that FGF/MAPK blockade may be particularly efficacious against mPCs with an AR-null phenotype.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Transdução de Sinais
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Receptores Androgênicos
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Fatores de Crescimento de Fibroblastos
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article