Renin-angiotensin system: role in the development and progression of prostate cancer

Being the most common malignancy in men, prostate cancer (PCa) is a significant social and medical problem. The development of new approaches to the diagnosis, prognosis, and treatment of PCa is one of the most important tasks of current urological oncology.The renin-angiotensin cascade plays a crucial role in the regulation of most physiological and pathophysiological conditions in the human organism, including vascular tone, blood pressure, development and progression of atherosclerosis, and key metabolic processes. The classical regulation axis of the renin-angiotensin system (RAS) is well known and includes angiotensin converting enzyme (ACE)/angiotensin II/ angiotensin II receptors. Recently, new RAS elements have been found and described, such as ACE2 (homologue of ACE), angiotensin isoforms 1—7, alamandin, etc. This resulted in the discovery of many new alternative axes of RAS regulation, including ACE2/angiotensin-(1—7)/ MAS receptor, prorenin/(pro)renin receptor/MAP kinase, and angiotensin A/almandin/receptor D (MrgD). The prostate gland has a local RAS; all main components of RAS are expressed in prostate tissues.This review analyzes molecular mechanisms underlying carcinogenic effects of RAS, as well as classical and alternative pathways of RAS regulation in PCa. We have described the results of studies evaluating individual RAS parameters in PCa, which confirm the existence of a complex network between various elements of local RAS and molecular and cellular mechanisms of prostate carcinogenesis. RAS has been proved to play an important role in PCa development and progression.We have also covered new therapeutic targets for PCa treatment, presumable mechanisms of action, and prospects of using RAS inhibitors for PCa.