ArticleJournal of gynecologic oncology2025
Investigation of selective glucocorticoid receptor modulation in high-grade serous ovarian cancer PDX models.
Article in Journal of gynecologic oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Cost-effectiveness analysis of nab-paclitaxel with or without relacorilant for platinum-resistant ovarian cancer.Journal of ovarian research · 2026Article
- Context-dependent effect of glucocorticoid receptor activity shapes ovarian cancer cell plasticity and therapy response.Molecular cancer · 2026Article
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Authors and funding
13 authors.
Funding
Abstract
objectiveIn ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapy-induced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX).
methodsSix high-grade serous (HGS) OvCa PDX models expressing GR mRNA (
resultsOne of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response.
conclusionThe significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.
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