Targeting DUSP Activity as a Treatment for High-Grade Serous Ovarian Carcinoma.
Mol Cancer Ther
; 21(8): 1285-1295, 2022 08 02.
Article
en En
| MEDLINE
| ID: mdl-35587258
ABSTRACT
Identifying novel, durable treatments for high-grade serous ovarian cancer (HGSOC) is paramount to extend both progression-free survival (PFS) and overall survival (OS) in patients afflicted with this disease. Dual-specificity phosphatase 1 (DUSP1) was identified as one of seven genes that may significantly affect prognosis in patients with HGSOC; however, the role of DUSP inhibition (DUSPi) in the treatment of HGSOC remains largely unknown. In this study, we show that DUSP1 is highly expressed in HGSOC and confers worse PFS and OS. Further, we corroborate data that show DUSP1 expression is directly associated with therapy resistance. Using a tissue microarray of 137 different serous ovarian carcinomas, we demonstrate the high expression of DUSP1 in primary and recurrent serous ovarian cancer. In both acquired and de novo therapy HGSOC-resistant models, DUSPi both inhibited cellular proliferation and promoted cell death. RPPA analysis of HGSOC cells revealed DUSPi led to the differential regulation of several pathways, including AMPK and mTORC. Further, in a patient-derived xenograft HGSOC model, DUSPi significantly inhibited tumor progression.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Ováricas
/
Cistadenocarcinoma Seroso
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Mol Cancer Ther
Asunto de la revista:
ANTINEOPLASICOS
Año:
2022
Tipo del documento:
Article