Use of beta-blocker types and risk of incident prostate cancer in a multiethnic population

Zahalka, Ali H.; Fram, Ethan; Lin, Wilson; Mohn, Larkin; Frenette, Paul S.; Agalliu, Ilir; Watts, Kara

doi:10.1016/j.urolonc.2020.03.024

Cited by 14 publications

(6 citation statements)

References 26 publications

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“…Although the role of β-adrenergic receptors in lung cancer is not fully elucidated, several retrospective studies have investigated the correlation of incidental inhibition (i.e., patients who used β-blockers for the treatment of hypertension and/or cardiovascular diseases or anxiety) of these receptors with clinical outcomes in lung cancer. The potential of β-blockers to inhibit the growth of different types of tumors and, consequently, metastasis has been supported by in vitro and in vivo studies [ 24 , 61 , 62 ]. Additionally, the non-small-cell lung cancer (NSCLC) cell lines HT-29 and A549 treated with norepinephrine showed increased cellular migration, indicating a more invasive and metastatic phenotype, which was abrogated by propranolol [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Sympathetic Nervous System Impairs Prognosis in Lung Cancer Patients: A Scoping Review of Clinical Studies

Garramona,

Cunha,

Vieira

et al. 2023

Lung Cancer Manag.

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Aim: To summarize current knowledge, gaps, quality of the evidence and show main results related to the role of the autonomic nervous system in lung cancer. Methods: Studies were identified through electronic databases (PubMed, Scopus, Embase and Cochrane Library) in October 2023, and a descriptive analysis was performed. Twenty-four studies were included, and most were observational. Results: Our data indicated an increased expression of β-2-adrenergic receptors in lung cancer, which was associated with poor prognosis. However, the use of β-blockers as an add-on to standard treatment promoted enhanced overall survival, recurrence-free survival and reduced metastasis occurrence. Conclusion: Although the results herein seem promising, future research using high-quality prospective clinical trials is required to draw directions to guide clinical interventions.

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Section: Discussionmentioning

confidence: 99%

Increased Sympathetic Nervous System Impairs Prognosis in Lung Cancer Patients: A Scoping Review of Clinical Studies

Garramona,

Cunha,

Vieira

et al. 2023

Lung Cancer Manag.

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“…Propranolol is evaluated in combination with etodolac or alone as perioperative, while carvedilol is evaluated in patients with prostate cancer before surgery. A positive impact of other agents has been shown in a retrospective analysis showing that atenolol usage for an extended period significantly lowers prostate cancer incidence by more than 50% [ 115 ].…”

Section: Repurposing Of Anti-hypertensive and Anti-diabetic Drugs: Cu...mentioning

confidence: 99%

“…The most promising anti-diabetic agent for prostate cancer is metformin, with eight clinical trials, as a single treatment (Phase III, Figure 2 ) and Phase II (seven trials) either as a single therapy or combined with standard therapies ( Figure 5 A). Despite the controversial data about the association between metformin use and prostate cancer incidence or survival [ 115 ], research has shown that metformin reduces the risk of prostate cancer and improves survival due to its direct anti-cancer mechanisms or secondary effects from the improvement of metabolic syndrome [ 119 , 120 ]). Suggested direct anti-cancer mechanisms include liver kinase B1 (LKB1) and AMPK activation, inhibition of mTOR activity and protein synthesis, induction of apoptosis and autophagy by p53 and p21, and decreased blood insulin [ 120 ].…”

Section: Repurposing Of Anti-hypertensive and Anti-diabetic Drugs: Cu...mentioning

confidence: 99%

Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp

Hijazi

Gessner

El‐Najjar

2023

Cancers

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Despite the advancement in drug discovery for cancer therapy, drug repurposing remains an exceptional opportunistic strategy. This approach offers many advantages (faster, safer, and cheaper drugs) typically needed to overcome increased challenges, i.e., side effects, resistance, and costs associated with cancer therapy. However, not all drug classes suit a patient’s condition or long-time use. For that, repurposing chronically used medications is more appealing. This review highlights the importance of repurposing anti-diabetic and anti-hypertensive drugs in the global fight against human malignancies. Extensive searches of all available evidence (up to 30 March 2023) on the anti-cancer activities of anti-diabetic and anti-hypertensive agents are obtained from multiple resources (PubMed, Google Scholar, ClinicalTrials.gov, Drug Bank database, ReDo database, and the National Institutes of Health). Interestingly, more than 92 clinical trials are evaluating the anti-cancer activity of 14 anti-diabetic and anti-hypertensive drugs against more than 15 cancer types. Moreover, some of these agents have reached Phase IV evaluations, suggesting promising official release as anti-cancer medications. This comprehensive review provides current updates on different anti-diabetic and anti-hypertensive classes possessing anti-cancer activities with the available evidence about their mechanism(s) and stage of development and evaluation. Hence, it serves researchers and clinicians interested in anti-cancer drug discovery and cancer management.

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“…The use of video-microscopy and microarray analysis demonstrated that neurotransmitters like norepinephrine induces tumor cell migration in prostate cancer cells, supporting the use of β-blockers as a preventative measure for prostate cancer metastasis [ 60 ]. Clinically, the long-term usage [ 3 – 5 ] of atenolol may be beneficial in reducing the risk for prostate cancer, compared to those not on β-adrenoceptor antagonists or those taking other β-adrenoceptor antagonists, such as carvedilol and metoprolol [ 61 ]. A systematic literature review and meta-analysis of 16,825 patients found that exposure to β-adrenoceptor antagonists was associated with lower cancer-specific mortality in patients with prostate cancer.…”

Section: Significance Of Targeting Of Adrenergic Signaling Mechanismsmentioning

confidence: 99%

Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease

et al. 2021

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The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease.

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Use of beta-blocker types and risk of incident prostate cancer in a multiethnic population

Cited by 14 publications

References 26 publications

Increased Sympathetic Nervous System Impairs Prognosis in Lung Cancer Patients: A Scoping Review of Clinical Studies

Increased Sympathetic Nervous System Impairs Prognosis in Lung Cancer Patients: A Scoping Review of Clinical Studies

Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp

Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease

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