Unraveling the Role of Glucocorticoid Receptor in Inflammation and Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 990

Special Issue Editor


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Guest Editor
Institute of Chemical Biology, National Hellenic Research Foundation, Athens, Greece
Interests: glucocorticoid receptor in inflammation and cancer; estrogen receptor beta in breast cancer prognosis and treatment; natural and synthetic agents for preventing and/or treating endocrine disorders; hazard assessment of endocrine-disrupting chemicals

Special Issue Information

Dear Colleagues,

Glucocorticoids (GCs) are steroid hormones that regulate a variety of physiological processes, including development, metabolism, homeostasis, immune response, and apoptosis in a cell-specific manner. The biological actions of GCs are mediated through the ubiquitously expressed glucocorticoid receptor (GR), a ligand-inducible transcription factor that is activated upon GC binding and regulates the transcription of hundreds of target genes.

GC-activated GR is implicated in various diseases, ranging from inflammatory and metabolic disorders to cancer. GCs are widely used as potent anti-inflammatory drugs for the treatment of inflammatory and autoimmune diseases. Under physiological conditions, GCs also exert pro-inflammatory effects. These apparently opposite actions seem to work together to prepare the immune response under stress conditions (pro-inflammatory), subsequently controlling the response (anti-inflammatory) and restoring homeostasis.

Inflammation is known to predispose the development and promote the progression of various types of cancer. The glucocorticoid regulation of tumor-promoting inflammation and anti-tumor immunity affects cancer development. Despite the extensive clinical use of GCs to alleviate the side effects of chemotherapy, the role of GR in cancer initiation, progression, and therapy remains elusive. GCs have been used for the treatment of various hematological cancers; however, their role in different types of solid cancers is not clearly defined. GC signaling through GR may either suppress or promote tumor development in a cancer type-specific manner.

The clinical use of GC is often accompanied with adverse side effects. Nevertheless, the therapeutic usage of GCs is continuously rising. At present, there is an unmet need for novel selective GR agonists/modulators (SEGRA/SEGRM) favoring the therapeutic action of GCs over the undesirable side effects. Such ligands could improve the clinical performance of long-term treatments with GCs, where adverse side effects should be taken into consideration.

This Special Issue aims to unravel the role of GCs and GR in inflammation and cancer initiation, progression, and treatment. New studies are expected to shed light on the molecular and cellular mechanisms underlying the anti-/pro-inflammatory and tumor-suppressive/oncogenic action of GR. Studies on novel agonists/modulators with an improved therapeutic index as compared to classical GCs are also welcome.

Dr. Dimitra Mitsiou
Guest Editor

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Keywords

  • glucocorticoids
  • glucocorticoid receptor
  • inflammation
  • anti-inflammatory action
  • pro-inflammatory action
  • cancer
  • tumor-promoting inflammation
  • onco-suppressive action
  • oncogenic action
  • selective glucocorticoid receptor agonists/modulators

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Published Papers (1 paper)

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Review

16 pages, 1060 KiB  
Review
Glucocorticoid Insensitivity: Is It a Question of Time and Place?
by Christopher Lambers and Michael Roth
Biomedicines 2025, 13(6), 1418; https://doi.org/10.3390/biomedicines13061418 - 10 Jun 2025
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Abstract
Background: Glucocorticoid insensitivity is a problem for the therapy of chronic inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Both are non-communicable chronic inflammatory lung diseases with worldwide increasing incidences. Only symptoms can be controlled by inhaled or systemic [...] Read more.
Background: Glucocorticoid insensitivity is a problem for the therapy of chronic inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Both are non-communicable chronic inflammatory lung diseases with worldwide increasing incidences. Only symptoms can be controlled by inhaled or systemic glucocorticoids, often combined with β2 agonists and/or muscarinic receptor antagonists. The therapeutic effect of glucocorticoids varies between individuals, and a significant number of patients do not respond well. It is believed that only protein-free circulating unbound glucocorticoids can enter cells by diffusion and achieve their therapeutic effect by binding to the intracellular glucocorticoid receptor (GR), encoded by the NR3C1 gene, for which over 3000 single-nucleotide polymorphisms have been described. In addition, various GR protein isoforms result from 11 transcription start sites, and differential mRNA splicing leads to further GR protein variants; each can be modified post-translational and alter steroid response. To add more variety, some GR isoforms are expressed cell-type specific or in a sub-cellular location. The GR only functions when it forms a complex with other intracellular proteins that regulate ligand binding, cytosol-to-nuclear transport, and nuclear and cytosolic action. Importantly, the timing of the GR activity can be cell type, time, and condition specific. These factors are rarely considered when assessing disease-specific loss or reduced GR response. Conclusions: Future studies should analyze the timing of the availability, activity, and interaction of all components of the glucocorticoid signaling cascade(s) and compare these factors between non-diseased and diseased probands, applying the combination of all omics methods (250). Full article
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