Abstract
Breast cancer (BC) is associated with multiple molecular factors such as overexpression of the beta-2 adrenergic receptor (ADRB2) and the overproduction of its agonists (norepinephrine and epinephrine). The role of adrenergic signaling in BC highlights the therapeutic potential of non-selective beta-blockers (nsBBs) as inhibitors of well-established protumor signaling pathways related to ADRB2 and their possible affinity for other important protumoral receptors. Our aim was to identify how nsBBs currently prescribed may also interact with receptors other than ADRB2, which are related to the pathophysiology of BC, using bioinformatic intracellular pathway analysis (BIPA). Subsequently, the affinity of nsBBs for both ADRB2 and the targets identified by BIPA was evaluated. We found that, beyond ADRB2, both receptor tyrosine kinase 2 (ERBB2) and neuropeptide Y receptor (NPYR) are promising targets for nsBBs in the adjuvant treatment of BC, according to BIPA. Docking studies showed that the nsBB with the highest binding affinity (ΔG) was carvedilol (-10.5 kcal/mol), followed by propranolol (-8.5 kcal/mol). These in silico findings suggest previously unrecognized pharmacological mechanisms for nsBBs in the possible treatment for BC. Notably, differences in receptor affinity were observed among the nsBBs, with carvedilol exhibiting the strongest binding affinity values on ADRB2, ERBB2, and NPYR as biological targets against BC cells. These promising results require future experimental validation.