β-Adrenergic Signaling in Lung Cancer: A Potential Role for Beta-Blockers

Lung cancer results in more patient deaths each year than any other cancer type. Additional treatment strategies are needed to improve clinical responses to approved treatment modalities and prevent the emergence of resistant disease. Catecholamines including norepinephrine and epinephrine are elevated as a result of chronic stress and mediate their physiological effects through activation of adrenergic receptors on target tissues. Lung cancer cells express β-adrenergic receptors (β-ARs), and numerous preclinical studies indicate that β2-AR signaling on lung cancer cells facilities cellular programs including proliferation, motility, apoptosis resistance, epithelial-to-mesenchymal transition, metastasis, and the acquisition of an angiogenic and immunosuppressive phenotype. Here, we review the preclinical and clinical evidence supporting a potential role for beta-blockers in improving the clinical outcome of lung cancer patients. Graphical Abstract Catecholamines including norepinephrine and epinephrine act of β-ARs expressed on NSCLC tumor cells and activate pathways regulating tumor progression.