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Androgen Dependent and Hormone Refractory Prostate Cancer
Cancer of the prostate is the second highest cause of cancer deaths in men in the United States. It is estimated that approximately one in five men will be diagnosed with prostate cancer during their lifetime and one in 33 will die of the disease. Since the majority of prostate cancers require the male hormone androgen in order to grow, a standard treatment for advanced disease is androgen ablation or blockade. Androgen ablation will block the action of androgen released from the testes and adrenal gland, and can be achieved by administration of drugs such as Zoladex and Casodex. As side-effects can occur, these drugs must be taken under medical supervision. Hormone treatment may be in tablet form, or alternatively by injections and implants. Other treatments commonly used to treat prostate cancer include surgery, chemotherapy, radiotherapy and cryotherapy.
Measurement of prostate-specific antigen (PSA), a tumor marker, is commonly used to monitor patients with prostate cancer because expression of the PSA gene is affected by androgen levels.
Patients often enter a period of remission after hormone treatment which can last up to 3 years. Unfortunately, advanced stage prostate cancer generally becomes insensitive to androgen ablation (hormone refractory prostate cancer, HRPC) and patients often die from the disease spreading to other organs (metastases).
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Hydrocortisone as a Treatment for Prostate Cancer
Glucocorticoids such as hydrocortisone, prednisone and dexamethasone can be clinically useful in relapsed HRPC patients. Glucocorticoids are commonly prescribed as an antiemetic (to prevent nausea and vomiting) in cancer patients receiving chemotherapy or radiotherapy. Currently, paclitaxel and dexamethasone in combination is a standard treatment for HRPC. Clinical trials investigating GCs, such as hydrocortisone, as a treatment for prostate cancer have shown reductions in PSA levels of between 20–80% depending on the type and dosage of GC used.
Although glucocorticoids are accepted as a treatment for HRPC, their exact mechanism of action is not known. Evidence suggests that GCs exert effects on certain biological processes such as angiogenesis (formation of new blood vessels), lymph production, cell death, cytokines and growth factors. All of these factors are thought to be important in the transition of prostate cancer from androgen dependent to hormone refractory.
More research is required to fully understand the effects of GCs on the various biological pathways in prostate cancer. The use of the gene and protein expression microarray technology is likely to provide invaluable information in this field. Hopefully this will aid the future development of new therapies for hormone refractory prostate cancer.
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Glucocorticoid receptor signaling and prostate cancer by E.Kassi and P.Moutsatsou. Cancer Letters, Volume 302, Issue 1, 1 March 2011, Pages 1-10
Glucocorticoids Suppress Tumor Lymphangiogenesis of Prostate Cancer Cells by Akihiro Yano, Yasuhisa Fujii, Aki Iwai, Satoru Kawakami, Yukio Kageyama and Kazunori Kihara. Clinical Cancer Research October, 2006 vol 12; Page 6012
Cancer Research UK - www.cancerhelp.org.uk