Unraveling the Role of Glucocorticoid Receptor in Inflammation and Cancer

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