Novel therapeutic agents targeting the glucocorticoid receptor for inflammation and cancer.
Sommer P., Ray DW.
Glucocorticoids, through their interaction with the ubiquitous glucocorticoid receptor (GR), have extensive and disparate effects on different cells and tissues. They have long been used in the treatment of asthma, arthritis and autoimmune diseases based on their anti-inflammatory and immunosuppressive effects. For these reasons, as well as for their ability to induce massive apoptosis in hematological malignancies, they are also commonly used as cotreatment in cancers. Despite their wide usage, chronic glucocorticoid therapy has deleterious side effects, including weight gain, osteoporosis and diabetes mellitus, and has been shown to diminish the tumor toxicity of chemotherapy, preventing the full potential of glucocorticoid treatment from being realized. Technological advances have contributed to a better understanding of the mechanism of glucocorticoid action, prompting the development of tailored therapeutics targeting the desired outcomes of GR signaling. This review discusses recent advances in the development of novel therapeutic agents for inflammation and cancer through targeting the GR.