Journal
JOURNAL OF UROLOGY
Volume 192, Issue 1, Pages 16-23Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.juro.2014.01.114
Keywords
prostate; prostatic hyperplasia; 5-alpha reductase inhibitors; finasteride; individualized medicine
Categories
Funding
- [NIH-R01DK091353]
Ask authors/readers for more resources
Purpose: Benign prostatic hyperplasia affects more than 50% of men by age 60 years, and is the cause of millions of dollars in health care expenditure for the treatment of lower urinary tract symptoms and urinary obstruction. Despite the widespread use of medical therapy, there is no universal therapy that treats all men with symptomatic benign prostatic hyperplasia. At least 30% of patients do not respond to medical management and a subset require surgery. Significant advances have been made in understanding the natural history and development of the prostate, such as elucidating the role of the enzyme 5 alpha-reductase type 2, and advances in genomics and biomarker discovery offer the potential for a more targeted approach to therapy. We review the current understanding of benign prostatic hyperplasia progression as well as the key genes and signaling pathways implicated in the process such as 5 alpha-reductase. We also explore the potential of biomarker screening and gene specific therapies as tools to risk stratify patients with benign prostatic hyperplasia and identify those with symptomatic or medically resistant forms. Materials and Methods: A PubMed (R) literature search of current and past peer reviewed literature on prostate development, lower urinary tract symptoms, benign prostatic hyperplasia pathogenesis, targeted therapy, biomarkers, epigenetics, 5 alpha-reductase type 2 and personalized medicine was performed. An additional Google Scholar (TM) search was conducted to broaden the scope of the review. Relevant reviews and original research articles were examined, as were their cited references, and a synopsis of original data was generated with the goal of informing the practicing urologist of these advances and their implications. Results: Benign prostatic hyperplasia is associated with a state of hyperplasia of the stromal and epithelial compartments, with 5 alpha-reductase type 2 and androgen signaling having key roles in the development and maintenance of the prostate. Chronic inflammation, multiple growth factor and hormonal signaling pathways, and medical comorbidities have complex roles in prostate tissue homeostasis as well as its evolution into the clinical state of benign prostatic hyperplasia. Resistance to medical therapy with finasteride may occur through silencing of the 5 alpha-reductase type 2 gene by DNA methylation, leading to a state in which 30% of adult prostates do not express 5 alpha-reductase type 2. Novel biomarkers such as single nucleotide polymorphisms may be used to risk stratify patients with symptomatic benign prostatic hyperplasia and identify those at risk for progression or failure of medical therapy. Several inhibitors of the androgen receptor and other signaling pathways have recently been identified which appear to attenuate benign prostatic hyperplasia progression and may offer alternative targets for medical therapy. Conclusions: Progressive worsening of lower urinary tract symptoms and bladder outlet obstruction secondary to benign prostatic hyperplasia is the result of multiple pathways including androgen receptor signaling, proinflammatory cytokines and growth factor signals. New techniques in genomics, proteomics and epigenetics have led to the discovery of aberrant signaling pathways, novel biomarkers, DNA methylation signatures and potential gene specific targets. As personalized medicine continues to develop, the ability to risk stratify patients with symptomatic benign prostatic hyperplasia, identify those at higher risk for progression, and seek alternative therapies for those in whom conventional options are likely to fail will become the standard of targeted therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available