ArticleHormones & cancer2014
Glucocorticoid receptor activity contributes to resistance to androgen-targeted therapy in prostate cancer.
Article in Hormones & cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03863145 (Open Label, Multicenter, Phase 1 Study to Evaluate the Maximum Tolerated Dose of Orally Administered CB-03-10 With Dose Expansion Phase, in Subjects With Advanced Solid Tumors), which is not on this map. Cited by 165 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Open Label, Multicenter, Phase 1 Study to Evaluate the Maximum Tolerated Dose of Orally Administered CB-03-10 With Dose Expansion Phase, in Subjects With Advanced Solid Tumors
Who cites it
165 citing papers in PubMed, 274 citations in OpenAlex.
- Relacorilant plus nab-paclitaxel for the treatment of metastatic pancreatic ductal adenocarcinoma: results from the open-label RELIANT study.The oncologist · 2024Trial
- Phase I/II Trial of Enzalutamide and Mifepristone, a Glucocorticoid Receptor Antagonist, for Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Trial
- Evaluation of Intense Androgen Deprivation Before Prostatectomy: A Randomized Phase II Trial of Enzalutamide and Leuprolide With or Without Abiraterone.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- Trial
- Docosahexaenoic Acid Enhances the Cytotoxic Effects of Enzalutamide and the PARP Inhibitor in Castration-Resistant Prostate Cancer Cell Lines.International journal of molecular sciences · 2026Article
- Article
- TMPRSS2-ERG confers resistance of prostate cancer to antiandrogens.EMBO molecular medicine · 2026Article
- High level expression of glucocorticoid receptor (GR) is linked to aggressive tumor features, early biochemical recurrence, and genetic instability in prostate cancer.Prostate cancer and prostatic diseases · 2026Article
- Phosphorylation of UDP-glucose dehydrogenase increases glycosaminoglycan biosynthesis and promotes tumor cell motility, spheroid growth, and therapeutic resistance.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Article
- Novel hormone therapies for advanced prostate cancer: Understanding and countering drug resistance.Journal of pharmaceutical analysis · 2025Review
- SLC7A11 upregulation via AR and NEDD4L ubiquitination contributes to ferroptosis inhibition and enzalutamide resistance in castration-resistant prostate cancer.Cell death & disease · 2025Article
- Chronic stress: a fourth etiology in tumorigenesis?Molecular cancer · 2025Review
- Glucocorticoid Receptor (GR) Expression in Human Tumors: A Tissue Microarray Study on More than 14,000 Tumors.Biomedicines · 2025Article
- A TBX2-driven signaling switch from androgen receptor to glucocorticoid receptor confers therapeutic resistance in prostate cancer.Oncogene · 2025Article
- The Homeobox Transcription Factor NKX3.1 Displays an Oncogenic Role in Castration-Resistant Prostate Cancer Cells.Cancers · 2025Article
- Review
- Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment.Expert review of anticancer therapy · 2024Review
- ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors.Cancer research communications · 2024Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Despite new treatments for castrate-resistant prostate cancer (CRPC), the prognosis of patients with CRPC remains bleak due to acquired resistance to androgen receptor (AR)-directed therapy. The glucocorticoid receptor (GR) and AR share several transcriptional targets, including the anti-apoptotic genes serum and glucocorticoid-regulated kinase 1 (SGK1) and Map kinase phosphatase 1 (MKP1)/dual specificity phosphatase 1 (DUSP1). Because GR expression increases in a subset of primary prostate cancer (PC) following androgen deprivation therapy, we sought to determine whether GR activation can contribute to resistance to AR-directed therapy. We studied CWR-22Rv1 and LAPC4 AR/GR-expressing PC cell lines following treatment with combinations of the androgen R1881, AR antagonist MDV3100, GR agonist dexamethasone, GR antagonists mifepristone and CORT 122928, or the SGK1 inhibitor GSK650394. Cell lines stably expressing GR (NR3C1)-targeted shRNA or ectopic SGK1-Flag were also studied in vivo. GR activation diminished the effects of the AR antagonist MDV3100 on tumor cell viability. In addition, GR activation increased prostate-specific antigen (PSA) secretion and induced SGKI and MKP1/DUSP gene expression. Glucocorticoid-mediated cell viability was diminished by a GR antagonist or by co-treatment with the SGK1 inhibitor GSK650394. In vivo, GR depletion delayed castrate-resistant tumor formation, while SGK1-Flag-overexpressing PC xenografts displayed accelerated castrate-resistant tumor initiation, supporting a role for SGK1 in GR-mediated CRPC progression. We studied several PC models before and following treatment with androgen blockade and found that increased GR expression and activity contributed to tumor-promoting PC cell viability. Increased GR-regulated SGK1 expression appears, at least in part, to mediate enhanced PC cell survival. Therefore, GR and/or SGK1 inhibition may be useful adjuncts to AR blockade for treating CRPC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.