Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

Abstract

There is growing evidence that the neurotransmitter norepinephrine (NE) and its sister molecule epinephrine (EPI) (adrenaline) affect some types of cancer. Several recent epidemiological studies have shown that chronic use of beta blocking drugs (which antagonize NE/EPI receptors) results in lower recurrence, progression, or mortality of breast cancer and malignant melanoma. Preclinical studies have shown that manipulation of the levels or receptors of NE and EPI with drugs affects experimentally induced cancers. Psychological stress may play an etiological role in some cases of cancer (which has been shown epidemiologically), and this could be partly mediated by NE and EPI released by the sympathetic nervous system as part of the body’s “fight or flight” response. A less well-appreciated phenomenon is that the genetic tone of NE/EPI may play a role in cancer. NE and EPI may affect cancer by interacting with molecular pathways already implicated in abnormal cellular replication, such as the P38/MAPK pathway, or via oxidative stress. NE/EPI-based drugs other than beta blockers also may prevent or treat various types of cancer, as may cholinesterase inhibitors that inhibit the sympathetic nervous system, which could be tested epidemiologically.

A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response

“…Further, intriguing epidemiological evidence has shown that patients taking drugs known as β-adrenergic antagonists (“β-blockers”), which are commonly prescribed to treat hypertension and anxiety, have significantly lower rates of several cancers [4–8]. As will be discussed, the anti-tumor effect of β-blockers involves the inhibition of multiple pro-survival pathways within tumor cells.…”

Significant Dietary Changes during Human Evolution and the Development of Cancer: From Cells in Trouble to Cells Causing Trouble

“…At present, a growing body of evidence suggests that NE plays a pivotal role in the progression of malignant tumors by modulating proliferation, angiogenesis, inflammation, macrophage infiltration, metastasis and inhibition of apoptosis, mediated to some extent through activation of various growth factors and cytokines [132][133][134][135].…”

Stress, Metabolism and Cancer

“…50–53 Moreover, use of both β-blockers and the α 1 -adrenergic antagonist, prazosin, which is prescribed for the treatment of benign prostatic hypertrophy, in mouse tumor models has been shown to inhibit proangiogenic cytokine production, decrease cell proliferation, and increase apoptosis. 54,55 Finally, studies reveal that taking β-blockers before surgery improves outcome.…”