Beta-Blockers as Anti-metastatic Drugs

SUMMARY



More than 90% of cancer deaths are caused by metastasis formation rather than the primary tumor [1]. Active migration of tumor cells is an essential prerequisite for invasion and metastasis formation. Norepinephrine is the most potent activator of cell migration as evidenced in colonic [2,20], mammary [3], and prostate [4] cancer cells. This increase is mediated predominantly by beta-2 adrenergic receptors and can therefore be inhibited by clinically established non-selective beta-blockers such as propranolol. The in vivo relevance of these experimental results was confirmed by mice xenograft models using prostate [5] and breast cancer [6]. Most strikingly, retrospective analyses of data from patients with several types of cancer showed that beta-blockers significantly reduce metastasis formation and consequently prolong the survival time of these patients. Results were obtained in epidemiological studies on breast cancer [7-10], melanoma [11-13], ovarian cancer [14], prostate cancer [15, 16], non-small cell lung cancer [17], and hepatocellular cancer [18] patients. Furthermore, a meta-analysis of these studies provided evidence that the use of beta-blockers can be associated with the prolonged survival of cancer patients, especially in patients with early-stage cancer treated primarily with surgery [19].

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