β-Adrenoceptors as drug targets in melanoma: novel preclinical evidence for a role of β3 -adrenoceptors.

Stress plays a role in tumourigenesis through catecholamines acting at β-adrenoceptors including β1-,β2- and β3-adrenoceptors, and the use of β-adrenoceptor antagonists seems to counteract tumour growth and progression. Preclinical evidence and meta-analysis data demonstrate that melanoma shows a positive response to β-adrenoceptor blockers and in particular to propranololacting mainly at β1-and β2-adrenoceptors. Although evidence suggesting that β3-adrenoceptors may play a role as a therapeutic target in infantile haemangiomas has been recently reviewed, a comprehensive analysis of the data available from preclinical studies supporting a possible role of β3-adrenoceptors in melanoma was not available. Here, we review data from the literaturedemonstrating that propranolol may be effective at counteracting melanoma growth, and we provide preclinical evidence that β3-adrenoceptors may also play a role in the pathophysiology of melanoma, thus opening the door for further clinical assays trying to explore β3-adrenoceptor blockers as novel alternatives for its treatment.