β-Adrenoceptors in Cancer: Old Players and New Perspectives

Handb Exp Pharmacol. 2023 Nov 21. doi: 10.1007/164_2023_701. Online ahead of print.

Abstract

Distress, or negative stress, is known to considerably increase the incidence of several diseases, including cancer. There is indeed evidence from pre-clinical models that distress causes a catecholaminergic overdrive that, mainly through the activation of β-adrenoceptors (β-ARs), results in cancer cell growth and cancer progression. In addition, clinical studies have evidenced a role of negative stress in cancer progression. Moreover, plenty of data demonstrates that β-blockers have positive effects in reducing the pro-tumorigenic activity of catecholamines, correlating with better outcomes in some type of cancers as evidenced by several clinical trials. Among β-ARs, β2-AR seems to be the main β-AR subtype involved in tumor development and progression. However, there are data indicating that also β1-AR and β3-AR may be involved in certain tumors. In this chapter, we will review current knowledge on the role of the three β-AR isoforms in carcinogenesis as well as in cancer growth and progression, with particular emphasis on recent studies that are opening new avenues in the use of β-ARs as therapeutic targets in treating tumors.

Keywords: Cancer cell proliferation; Carcinogenesis; Catecholamines; Dedifferentiation; Immune-tolerance; Stress; Tumor growth; Tumor infiltration; Tumor microenvironment.