Abstract
Androgens play a key role in the development and progression of prostate cancer, and androgen deprivation therapy (ADT) is the first line treatment for advanced disease. Although ADT is initially successful in controlling prostate cancer, many patients eventually become resistant to therapy and progress to develop lethal castration-resistant prostate cancer (CRPC). Androgens drive prostate cancer cell growth via the androgen receptor (AR), which is a transcription factor essential for prostate cancer cell viability, proliferation and invasion and has important roles in a range of signalling pathways. The progression to CRPC is thought to involve persistence of AR signalling and reprogramming of the AR transcriptional landscape to allow tumour cells to continue to grow despite low levels of circulating androgens. During this time AR activity can be maintained through activating mutations, gene amplification, AR splice variants or signalling crosstalk with other pathways. CRPC is highly aggressive and ultimately lethal, meaning there is an urgent need to understand the mechanisms that drive this form of the disease and to develop new therapeutic targets. This review discusses the role of the AR signalling in some of the many mechanisms and pathways that contribute to the development of prostate cancer and the progression to castrate resistant disease.
Highlights
androgen deprivation therapy (ADT) is initially successful in controlling prostate cancer, many patients eventually become resistant to therapy and progress to develop lethal castration-resistant prostate cancer (CRPC)
Gene amplification and copy number variations in both androgen receptor (AR) and CYP17A1 have been detected in circulating tumour cells (CTCs) and cell-free tumour DNA from metastatic CRPC patients indicating a possible mechanism for the resistance to treatment with second generation therapies [100,101,102,103]
There are a significant proportion of patients that go on to develop CRPC, in which Prostate cancer (PCa) cells develop mechanisms which allow them to continue to grow despite depleted testosterone levels
Summary
The prostate is a small glandular organ situated within the pelvic cavity of males, beneath the bladder and surrounding the urethra. The main function of the prostate is to produce prostatic fluid, a component of semen which protects and enhances the survival of sperm cells. The mature prostate is divided into four distinct zones, the transition zone, the central zone, the peripheral zone and a fibromuscular stroma (Figure 1a). The transition, central and peripheral zones contain highly organised glandular epithelium structures separated by a fibromuscular stromal network [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
