WOMEN IN CANCER THEMATIC REVIEW: Circadian rhythmicity and the influence of ‘clock’ genes on prostate cancer
| Autor: | Paramita M. Ghosh, Zsofia Kiss |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Endocrinology Diabetes and Metabolism Circadian clock CLOCK Proteins melatonin Medical and Health Sciences Androgen deprivation therapy Melatonin 03 medical and health sciences 0302 clinical medicine Endocrinology bmal1 Circadian Clocks androgen receptor Internal medicine circadian clock medicine Animals Humans Oncology & Carcinogenesis Circadian rhythm business.industry Prostatic Neoplasms Biological Sciences Circadian Rhythm PER2 Androgen receptor CLOCK Oncology 030220 oncology & carcinogenesis Female per1 business 030217 neurology & neurosurgery medicine.drug PER1 |
| Zdroj: | Endocrine-related cancer, vol 23, iss 11 |
| ISSN: | 1479-6821 1351-0088 |
| Popis: | The androgen receptor (AR) plays a key role in the development and progression of prostate cancer (CaP). Since the mid-1990s, reports in the literature pointed out higher incidences of CaP in some select groups, such as airline pilots and night shift workers in comparison with those working regular hours. The common finding in these ‘high-risk’ groups was that they all experienced a deregulation of the body’s internal circadian rhythm. Here, we discuss how the circadian rhythm affects androgen levels and modulates CaP development and progression. Circadian rhythmicity of androgen production is lost in CaP patients, with the clock genes Per1 and Per2 decreasing, and Bmal1 increasing, in these individuals. Periodic expression of the clock genes was restored upon administration of the neurohormone melatonin, thereby suppressing CaP progression. Activation of the melatonin receptors and the AR antagonized each other, and therefore the tumour-suppressive effects of melatonin and the clock genes were most clearly observed in the absence of androgens, that is, in conjunction with androgen deprivation therapy (ADT). In addition, a large-scale study found that high-dose radiation was more effective in CaP patients when it was delivered before 17:00 h, compared with those delivered after 17:00 h, suggesting that the therapy was more effective when delivered in synchrony with the patient’s circadian clock. As CaP patients are shown to become easily resistant to new therapies, perhaps circadian delivery of these therapeutic agents or delivery in conjunction with melatonin and its novel analogs should be tested to see if they prevent this resistance. |
| Databáze: | OpenAIRE |
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