Infantile Hemangiomas, Retinopathy of Prematurity and Cancer: A Common Pathogenetic Role of the β‐Adrenergic System

The serendipitous demonstration that the nonselective β‐adrenergic receptor (β‐AR) antagonist propranolol promotes the regression of infantile hemangiomas (IHs) aroused interest around the involvement of the β‐adrenergic system in angiogenic processes. The efficacy of propranolol was related to the β2‐AR blockade and the consequent inhibition of the production of vascular endothelial growth factor (VEGF), suggesting the hypothesis that propranolol could also be effective in treating retinopathy of prematurity (ROP), a retinal pathology characterized by VEGF‐induced neoangiogenesis. Consequent to the encouraging animal studies, a pilot clinical trial showed that oral propranolol protects newborns from ROP progression, even though this treatment is not sufficiently safe. Further, animal studies clarified the role of β3‐ARs in the development of ROP and, together with several preclinical studies demonstrating the key role of the β‐adrenergic system in tumor progression, vascularization, and metastasis, prompted us to also investigate the participation of β3‐ARs in tumor growth. The aim of this review is to gather the recent findings on the role of the β‐adrenergic system in IHs, ROP, and cancer, highlighting the fact that these different pathologies, triggered by different pathogenic noxae, share common pathogenic mechanisms characterized by the presence of hypoxia‐induced angiogenesis, which may be contrasted by targeting the β‐adrenergic system. The mechanisms characterizing the pathogenesis of IHs, ROP, and cancer may also be active during the fetal–neonatal development, and a great contribution to the knowledge on the role of β‐ARs in diseases characterized by chronic hypoxia may come from research focusing on the fetal and neonatal period.