Related Experiment Video
Updated: May 23, 2026
13:22
A Chemical Screening Procedure for Glucocorticoid Signaling with a Zebrafish Larva Luciferase Reporter System
Published on: September 10, 2013
Signaling Under Stress: Targeting the Glucocorticoid Receptor in Cancer
Melanie S Flint1, David M O'Malley2, Domenica Lorusso3,4
1School of Applied Sciences, University of Brighton, Brighton, United Kingdom.
Cancer Research
|May 22, 2026
Summary
Selective glucocorticoid receptor antagonists (SGRAs) enhance cancer therapies by blocking survival signals and improving responses to chemotherapy and immunotherapy. Clinical trials confirm SGRAs improve efficacy in ovarian cancer and show potential in prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Glucocorticoid receptor (GR) signaling is crucial for physiology but often dysregulated in cancer.
- Tumors hijack GR signaling for survival, growth, metastasis, immune evasion, and treatment resistance.
- Elevated GR signaling correlates with poor responses to various cancer treatments.
Purpose of the Study:
- To summarize the role of GR signaling in solid tumor biology.
- To provide mechanistic insights into how selective GR antagonists (SGRAs) impact cancer.
- To highlight clinical advances and outstanding questions regarding GR antagonism in cancer therapy.
Main Methods:
- Review of translational and non-clinical data on GR signaling in cancer.
- Analysis of clinical trial outcomes involving SGRAs and anti-cancer agents.
- Examination of molecular mechanisms of SGRA action, including downregulation of SGK1 and DUSP1.
Main Results:
- SGRAs synergize with chemotherapy (taxanes), targeted therapy (androgen receptor inhibitors, PARP inhibitors), and immunotherapy (anti-PD(L)-1).
- SGRAs exhibit tumor-intrinsic anti-apoptotic effects, downregulating SGK1 and DUSP1 to overcome cytotoxic chemotherapy resistance.
- Randomized controlled trials demonstrated improved efficacy of SGRAs combined with taxanes in platinum-resistant ovarian cancer.
- SGRAs show potential to inhibit GR-mediated resistance to anti-androgen therapy in prostate cancer.
Conclusions:
- Glucocorticoid signaling plays a significant role in solid tumor progression and treatment resistance.
- Selective GR antagonists represent a promising therapeutic strategy to enhance existing anti-cancer treatments.
- Further translational and clinical research is needed to fully elucidate the potential of SGRAs in diverse solid tumors.
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