Emerging role of glucocorticoid receptor in castration resistant prostate cancer: A potential therapeutic target

Glucocorticoids are used as co-medication with chemotherapy for solid tumors to reduce inflammation as well as cytotoxic side effects and are effective in easing symptoms related to chemotherapy. However, emerging evidence suggests that glucocorticoids may contribute to failure of chemotherapy and tumor progression of castration resistant prostate cancer (CRPC). Thus, in recent years, glucocorticoid signaling pathway has become an important therapeutic target for CRPC. Understanding the exact mechanism of GR actions in CRPC is still work in progress. There are studies suggesting that GR expression can be upregulated following antiandrogen therapy and can contribute to resistance to hormone therapies. Therefore, attempts are being made to develop selective glucocorticoid receptor modulators that specifically antagonize GR activity in CRPC, and thereby provide clinical benefit by blocking the GR mechanism for tumor growth. However, more targeted approaches are needed to understand the role of the GR-mediated target gene expressions in the CRPC that could in near future lead to better therapeutic options for patients with CRPC. This review highlights current perspectives on the actions of glucocorticoids during tumor progression and metastasis of CRPC.