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

Stress plays a role in tumorigenesis through catecholamines acting at β-adrenoceptors including β1-, β2- and β3-adrenoceptors and the use of β-adrenoceptor antagonists seems to counteract tumor growth and progression. Preclinical evidence and meta-analysis data demonstrate that melanoma shows a positive response to β-adrenoceptor blockers and in particular to propranolol acting mainly at β1- and β2-adrenoceptors. Although evidence suggesting that β3-adrenoceptors may play a role as a therapeutic target in infantile hemangiomas has been recently reviewed, a comprehensive analysis of the available data from preclinical studies supporting a possible role of β3-adrenoceptors in melanoma was not available. Here, we review literature data demonstrating that propranolol may be effective in 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.