Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer.
Cancer Cell
; 38(2): 279-296.e9, 2020 08 10.
Article
en En
| MEDLINE
| ID: mdl-32679108
ABSTRACT
Despite the development of second-generation antiandrogens, acquired resistance to hormone therapy remains a major challenge in treating advanced prostate cancer. We find that cancer-associated fibroblasts (CAFs) can promote antiandrogen resistance in mouse models and in prostate organoid cultures. We identify neuregulin 1 (NRG1) in CAF supernatant, which promotes resistance in tumor cells through activation of HER3. Pharmacological blockade of the NRG1/HER3 axis using clinical-grade blocking antibodies re-sensitizes tumors to hormone deprivation in vitro and in vivo. Furthermore, patients with castration-resistant prostate cancer with increased tumor NRG1 activity have an inferior response to second-generation antiandrogen therapy. This work reveals a paracrine mechanism of antiandrogen resistance in prostate cancer amenable to clinical testing using available targeted therapies.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Resistencia a Antineoplásicos
/
Neurregulina-1
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Microambiente Tumoral
/
Antagonistas de Andrógenos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos