The role of the β-
adrenoceptors (β-ARs) in
hypoxia-driven diseases has gained visibility after the demonstration that
propranolol promotes the regression of infantile
hemangiomas and ameliorates the signs of
retinopathy of prematurity (ROP). Besides the role of β2-ARs, preclinical studies in ROP have also revealed that β3-ARs are upregulated by
hypoxia and that they are possibly involved in
retinal angiogenesis. In a sort of figurative round trip, peculiarities typical of ROP, where
hypoxia drives
retinal neovascularization, have been then translated to
cancer, a disease equally characterized by
hypoxia-driven angiogenesis. In this step, investigating the role of β3-ARs has taken advantage of the assumption that
cancer growth uses a set of strategies in common with embryo development. The possibility that hypoxic induction of β3-ARs may represent one of the mechanisms through which primarily embryo (and then
cancer, as an astute imitator) adapts to grow in an otherwise hostile environment, has grown evidence. In both
cancer and embryo, β3-ARs exert similar functions by exploiting a metabolic shift known as the Warburg effect, by acquiring resistance against
xenobiotics, and by inducing a local immune tolerance. An additional potential role of β3-AR as a marker of stemness has been suggested by the finding that its antagonism induces
cancer cell differentiation evoking that β3-ARs may help
cancer to grow in a nonhospital environment, a strategy also exploited by embryos. From
cancer, the round trip goes back to
neonatal diseases for which new possible interpretative keys and potential pharmacological perspectives have been suggested.