Abstract
This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.
Highlights
Prostate cancer is the most commonly diagnosed male cancer in the world [1]
Of the fifty-four research articles identified only four studies examined the role of α-antagonists in prostate cancer (PCa) development in humans (Table 1)
Patients were treated for 6–11 months 4070 men were treated with α-antagonists for Benign prostatic hyperplasia or hypertension or HTN
Summary
Prostate cancer is the most commonly diagnosed male cancer in the world [1]. In Australia, prostate cancer account for approximately 30% of all newly diagnosed cancers and is the second most common cause of cancer-specific death in men [2]. In the United States, the non-selective doxazosin and terazosin are the most commonly prescribed α1-blockers due to their relatively long half-life [22,23] and clinically significant improvement in BPH-related LUTS These drugs have been associated with fewer adverse drug-related cardiovascular side effects, compared to prazosin [24]. In the late 1990s, monotherapy with α-antagonists was shown to provide long-term clinical benefits that could not be explained solely by acute prostatic relaxation [25,26,27] In support of these findings, a more recent study uncovered a large proportion of men (70%) experienced continued improvement of BPH-associated LUTS following discontinuation of α-antagonists [28]. This review will colligate the anticancer mechanisms of α-antagonists, evaluate the evidence supporting clinical anticancer efficacy of these drugs in PCa, and evaluate the evidence for use of these drugs in other cancers
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.
