The glucocorticoid receptor–autophagy axis in inflammation, immunoregulation, and cancer: a bidirectional regulatory network with therapeutic potential

Glucocorticoid receptor (GR) activation and autophagy are central regulators of cellular homeostasis and disease progression. However, the bidirectional interplay between GR signaling and autophagy remains incompletely understood, limiting context-specific insights and the translation of glucocorticoid-based therapies. This review synthesizes current knowledge of their molecular interactions, delineates the continuum from GR activation to the autophagy pathway, and discusses the integrated network governing their crosstalk. Notably, this axis exerts dual functions: it can promote survival or induce cell death, drive or resolve inflammation, and modulate therapeutic sensitivity depending on cellular context, disease state, and ligand characteristics. We review evidence on the GR–autophagy axis in immune cell function, cytokine dynamics, and inflammation control, and focus on its roles in inflammation and cancer pathogenesis, its therapeutic potential, and the challenges of clinical application. By integrating diverse research findings into a coherent framework, this review underscores the microenvironment’s influence on cancer regulatory mechanisms, highlights key therapeutic nodes, and advocates precise modulation of the GR–autophagy relationship as a promising therapeutic strategy.