Propranolol for the treatment of vascular sarcomas

Abstract

Vascular sarcomas are abnormal proliferations of endothelial cells. They range from benign hemangioma to aggressive angiosarcoma, and are characterized by dysregulated angiogenic signaling. Propranolol is a β-adrenergic receptor inhibitor that has demonstrated clinical efficacy in benign infantile hemangioma, and is now being used experimentally for more aggressive vascular sarcomas and other cancers. In this review, we discuss the use of propranolol in targeting these receptors in vascular tumors and other cancers.

Keywords: angiosarcoma; cancer; propranolol; vascular sarcoma; β-blocker.

Figure 1

Adrenergic signaling in the vascular tumor microenvironment. Notes: Epi and NE produced in sympathetic nerves act on β-adrenergic receptors present on T-cells, ECs, macrophages, and tumor cells. Activation of adrenergic receptors decreases infiltration by cytotoxic T-cells, increases the number of regulatory T-cells, and increases the recruitment and differentiation of tumor-associated macrophages. Sympathetic signaling also increases the migration and proliferation of normal ECs. In tumor cells, adrenergic signaling stimulates production of other proangiogenic and inflammatory mediators such as HIF-1α, VEGF, and IL-6 and suppresses the DNA damage response. Propranolol inhibits these oncogenic changes by blocking the β-receptors through which Epi and NE act. Abbreviations: Epi, epinephrine; NE, norepinephrine; EC, endothelial cell.