Beta Blockers and Melanoma

Abstract

Understanding the mechanisms of cancer immune-tolerance is one of the most important challenges. Several studies have demonstrated the potential anticarcinogenic effects of beta-blockers, in patients with prostate cancer, breast cancer, and melanoma. At the other side variety of dermatoses may be caused or aggravated by β-blockers-psoriasis, lichen planus-like drug eruptions (LDE), acrocyanosis, alopecia etc. Beta-blockers have been shown to improve the prognosis of melanoma patients significantly. Propranolol inhibits melanoma by downregulating the tumour angiogenesis but also tumour cell proliferation, invasiveness and local immune suppression. Studies showed that only β3-but, not β2-adrenoceptors, were up-regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub-populations including Treg, MDSC, and NK. They increased NK and CD8 number and cytotoxicity. Catecholamines may retard melanoma progression and that β-blockers may have unrecognised potential as a therapeutic intervention for melanoma, in the prevention of the growth of melanoma in all stages and as adjuvant therapy with other targeted and immune therapies for melanoma.

RETRACTED ARTICLE: β adrenergic receptor modulated signaling in glioma models: promoting β adrenergic receptor-β arrestin scaffold-mediated activation of extracellular-regulated kinase 1/2 may prove to be a panacea in the treatment of intracranial and spinal malignancy and extra-neuraxial carcinoma

“…Conformational protein modifications may differentially stabilize or destabilize binding between β adrenergic receptor carboxyl termini and β arrestin amino termini, thus generating differential effects upon desensitization, receptor endocytosis, and scaffold formation [11,12,14,16]. Rational drug design and mathematical models of βAR-drug binding will identify drug-specific and tumor cell-specific factors rendering β adrenergic receptor modulated signaling more likely to promote or inhibit cellular proliferation, unveil determinants contributing to preferential G s versus G i activation or inhibition, and identify optimal bio-organic compounds modulating the conformational state of β adrenergic receptors in staying the progression of glioblastoma [85,86,131,132]. Adenoviral transfection with chimeric constructs of β adrenergic receptors possessing carboxyl termini with high binding affinity to β arrestin amino termini and/or β arrestins possessing amino termini with high ligand binding affinity to GPCR carboxyl termini targeted specifically to glioma cells and high activity promoters may effectively preferentially promote scaffold-mediated activation of ERK1/2, blunting its nuclear translocation and retaining its cytosolic homeostatic effects, putatively proving to be a useful primary or adjuvant therapeutic approach enhancing the currently employed regimen of maximal safe resection, external beam radiotherapy, as well as concurrent and adjuvant temozolomide [21,153].…”

“…A study evaluating the utility of β antagonists excluding bevacizumab in patients with newly diagnosed low and high grade glioma sans multifocal disease or extra-neuraxial metastases may effectively unveil whether the observed effects are chiefly attributable to reducing angiogenesis [61]. β adrenergic receptor blockade significantly improves clinical outcomes and survival in patients harboring breast, ovarian, and prostate carcinoma and melanoma [131]. These agents reduce the risk of developing prostate carcinoma [132] and hepatocellular carcinoma in patients infected with hepatitis C [133] and prolong survival in patients with breast cancer [134].…”

Construction and validation of a prognostic risk model of angiogenesis factors in skin cutaneous melanoma

“…Pathological angiogenesis is a hallmark of cancer, targeting of the AFs have become a promising therapeutic strategy for melanoma. The reported therapeutic targets, such as integrins, vascular endothelial growth factor receptor ( VEGFR1-3 ), fibroblast growth factor receptor ( FGFR1-4 ), platelet-derived growth factor receptor α ( PDGFRα ), stem cell factor receptor ( KIT ), angiopoietin-2 ( ANGPT2 ), E-selectin, the transcription factor Yin Yang 1 ( YY1 ) and invasive endothelial cells (ECS) [ 16 – 20 ], can be inhibited by drugs like lenvatinib and propranolol, to delay tumor angiogenesis [ 17 , 21 ]. Additionally, many clinical studies are evaluating the therapeutic effect of angiogenesis inhibitors for patients with metastatic melanoma [ 22 ].…”

“…As shown in Figure 14, the high-risk group had more obvious levels of amplification and deletion than the low-risk group. AGING inhibited by drugs like lenvatinib and propranolol, to delay tumor angiogenesis [17,21]. Additionally, many clinical studies are evaluating the therapeutic effect of angiogenesis inhibitors for patients with metastatic melanoma [22].…”

Benefits of β-blockers in cancer treatment

“…Melanoma patients present a good response to propranolol treatment [41,42]. Propranolol decreases the level of VEGF, which plays a role in angiogenesis in melanoma cases.…”