title: Androgen-glucocorticoid interactions in the era of novel prostate cancer therapy.
abstract: Great strides have been made in the treatment of castration-resistant prostate cancer (CRPC) with the development of new antiandrogens (enzalutamide) and more potent androgen synthesis inhibitors (abiraterone) that have both improved patient outcomes. These new drugs have also helped unravel the complex biology of androgen-androgen receptor driven prostate cancer and brought into prominence various mechanisms triggering the development of drug resistance and tumour cell survival despite use of androgen deprivation therapy (ADT). The complex role of glucocorticoids in the treatment, management and progression of patients with CRPC is integral to these advances. Historically, glucocorticoid treatment has resulted in both subjective and objective responses in patients with advanced-stage prostate cancer. With the use of these new therapeutic agents, however, unexpected glucocorticoid-related mechanisms that can cause iatrogenic stimulation of prostate cancer growth have emerged, which might contribute to drug resistance and disease progression despite optimal ADT. For example, the upregulation of glucocorticoid receptors (GRs) during enzalutamide therapy results in glucocorticoid-GR-mediated regulation of androgen target genes, leading to escape from enzalutamide blockade. Thus, understanding the biological role of glucocorticoids in patients with prostate cancer is of major importance in the era of new and evolving antiandrogen therapies.
authors.affiliation: Stanford Cancer Centre, 875 Blake Wilbur Drive, Stanford, California 94305, USA.
authors.forename: Sujata
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Stanford Cancer Centre, 875 Blake Wilbur Drive, Stanford, California 94305, USA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: Division of Endocrinology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305-5103, USA.
authors.forename: David
authors.initials: D
authors.lastname: Feldman
mesh_terms: D000726:Androgen Antagonists / Q000378:metabolism* / Q000627:therapeutic use; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D005938:Glucocorticoids