Table of Contents  
Year : 2014  |  Volume : 16  |  Issue : 5  |  Page : 666

Reappraisal of glucocorticoids in castrate-resistant prostate cancer

1 Department of Urology and Medicine, Tulane Medical School, Tulane, New Orleans, Louisiana, USA
2 Department of Urology, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom

Date of Web Publication24-Jun-2014

Correspondence Address:
Oliver Sartor
Department of Urology and Medicine, Tulane Medical School, Tulane, New Orleans, Louisiana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1008-682X.133314

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Recent reports and discussions of preclinical prostate cancer models have emphasized the possibility that enzalutamide resistance may be mediated by glucocorticoid receptors (GR). [1],[2] In both in vitroand xenograft animal studies, it is possible to show that the GR is up-regulated in prostate cancer cell lines and that dexamethasone reverses enzalutamide induced growth inhibition. In these model systems, GR agonists can induce a subset of androgen receptor target genes including prostate-specific antigen. These investigators also report a correlation between GR expression in patient-derived prostate cancer specimens and clinical response to enzalutamide. The authors discuss the possibility that these findings have important clinical relevance. We note that the current clinical evidence for GR mediating drug resistance or disease progression in patients with castrate-resistant prostate cancer (CRPC) is very limited at best.

How to cite this article:
Sartor O, Parker CC, Bono JD. Reappraisal of glucocorticoids in castrate-resistant prostate cancer. Asian J Androl 2014;16:666

How to cite this URL:
Sartor O, Parker CC, Bono JD. Reappraisal of glucocorticoids in castrate-resistant prostate cancer. Asian J Androl [serial online] 2014 [cited 2021 Jul 23];16:666. Available from: - DOI: 10.4103/1008-682X.133314

Withdrawal responses to antiandrogens, progestins, and various estrogens are not uncommon in CRPC [3] suggesting that under certain circumstances a wide variety of compounds interacting with steroid receptors can stimulate cancer growth in patients. After a careful literature search, we are unable to find a single reported case of a pure glucocorticoid withdrawal response. We also note that a glucocorticoid antagonist clinical trial in CRPC found no responses. [4]

Moreover, various glucocorticoids including prednisone, prednisolone, hydrocortisone, and dexamethasone confer clinical benefit to prostate cancer patients, demonstrated by both tumor marker declines [5],[6],[7] and palliative assessments. [8] The exact mechanism whereby glucocorticoids exert their positive effect is unknown but inhibition of steroidogenesis in steroid synthesizing tissues has been postulated.

Glucocorticoids play a positive role in the clinic, whether used as monotherapy as cited above or in combination with established therapies such as abiraterone, docetaxel, or cabazitaxel. [9] Additional clinical data suggest that prednisolone and dexamethasone, though both GR agonists, are distinct in their effects thus mitigating arguments that these effects are solely GR mediated. [10]

Taken together, although there are multiple potential interactions between glucocorticoids and prostate cancer, the story may be quite complex and context dependent. Studies of the benefits and potential harms of various glucocorticoids are warranted in prostate cancer patients.

  References Top

1.Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell 2013; 155: 1309-22.  Back to cited text no. 1
2.Sharifi N. Steroid receptors aplenty in prostate cancer. N Engl J Med 2014; 370: 970-1.  Back to cited text no. 2
3.Scher HI, Zhang ZF, Nanus D, Kelly WK. Hormone and antihormone withdrawal: implications for the management of androgen-independent prostate cancer. Urology 1996; 47: 61-9.  Back to cited text no. 3
4.Taplin ME, Manola J, Oh WK, Kantoff PW, Bubley GJ, et al. A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones. BJU Int 2008; 101: 1084-9.  Back to cited text no. 4
5.Shamash J, Powles T, Sarker SJ, Protheroe A, Mithal N, et al. A multi-centre randomised phase III trial of Dexamethasone vs Dexamethasone and diethylstilbestrol in castration-resistant prostate cancer: immediate vs deferred Diethylstilbestrol. Br J Cancer 2011; 104: 620-8.  Back to cited text no. 5
6.Sartor O, Weinberger M, Moore A, Li A, Figg WD. Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer. Urology 1998; 52: 252-6.  Back to cited text no. 6
7.Dawson NA, Cooper MR, Figg WD, Headlee DJ, Thibault A, et al. Antitumor activity of suramin in hormone-refractory prostate cancer controlling for hydrocortisone treatment and flutamide withdrawal as potentially confounding variables. Cancer 1995; 76: 453-62.  Back to cited text no. 7
8.Tannock I, Gospodarowicz M, Meakin W, Panzarella T, Stewart L, et al. Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol 1989; 7: 590-7.  Back to cited text no. 8
9.Yap TA, Zivi A, Omlin A, de Bono JS. The changing therapeutic landscape of castration-resistant prostate cancer. Nat Rev Clin Oncol 2011; 8: 597-610.  Back to cited text no. 9
10.Lorente D, Weatherstone K, Omlin A, Pezaro C, Ferraldeschi R, et al. Tumor responses after steroid switch of prednisolone (P) to dexamethasone (D) in castration-resistant prostate cancer (CRPC) patients (pts) on abiraterone acetate (AA). European Cancer Congress; 2013. [Abstract 2918].  Back to cited text no. 10

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