The Potential Efficacy of β-Blockers on Melanoma Survival: A Narrative Review

April 2021 | Volume 20 | Issue 4 | Original Article | 380 | Copyright © April 2021


Published online March 30, 2021

Mohamad Goldust MDa, Zoe Apalla MDb, Jacek C. Szepietowski MDc, Mrinal Gupta MDd, Torello Lotti MDe

aDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
bSecond Dermatology Department, Aristotle University of Thessaloniki, Greece
cDepartment of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland
dDNB Dermatology Consultant Dermatologist, Treatwell Skin Centre, Jammu, India
eProfessor of Dermatology, University of Studies Guglielmo Marconi, Rome, Italy

Abstract
Melanoma is a common tumor accounting for around 3–5% of all cutaneous malignancies with worldwide increasing incidence. It is still associated with significant mortality despite the breakthrough of new innovative therapies within the last decade. A wide variety of treatment modalities is currently used for the management of melanoma, ranging from surgical excision of primary melanoma to adju-vant and palliative treatment with target molecules, including BRAF and MEK inhibitors, and immune checkpoint inhibitors. β-blockers have recently demonstrated in preclinical and clinical studies to reduce recurrence and to correlate with better overall survival in meta-static melanoma as an additional supportive treatment option, owing to their anti-tumor potential. Further investigation regarding their efficacy and safety profile is needed, since there are only few studies in the literature on this topic. Our aim is to evaluate the role and current status of β-blockers in melanoma management. The literature research includes peer-reviewed articles (clinical trials or scien-tific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) till May 2020 and reference lists of respective articles. Only articles published in English language were included.

J Drugs Dermatol. 20(4):380-383. doi:10.36849/JDD.5673

INTRODUCTION

Melanoma is a common malignant tumor derived from melanocytes. It accounts for only 3–5% of all cutaneous malignancies; however, about 70% of all skin cancer associated deaths globally are attributed to melanoma.1,2 There has been a marked change in melanoma treatment in the last decades. The novel standard treatment modality in high-risk melanoma patients who are sentinel positive is an adjuvant therapy with immune checkpoint inhibitors or targeted therapy with BRAF and MEK inhibitors over a period of one year.3 For patients with unresectable or metastatic melanomas, immune checkpoint inhibitors as combination therapy with PD-1 antibody nivolumab and CTLA-4 antibody ipilimumab or as monotherapy with PD-1 antibodies nivolumab or pembrolizumab are recommended as the first line treatment, whereas in BRAF-mutated patients BRAF and MEK inhibitors like dabrafenib and trametinib are additional treatment options.4-6 Despite the significant progress with their use, there are still certain limitations related to non-responders, loss of efficiency and acquired drug resistance especially in BRAF inhibitors that limits their utility.7 As melanoma is still associated with a poor survival rate despite the breakthrough of new innovative therapies within the last decade, as well as a significant impairment of the quality of life, it becomes important that further effective and safe therapies are developed. Various recent studies have reported a positive effect of β-blockers on the survival of melanoma patients.8-11

Since the advent of β-blockers, they have emerged as one of the most commonly used drugs in medicine. Pronethalol was the first clinically tested β-blocker, but due to its carcinogenic potential in mice, it was not approved for human use. Propranolol was the first β-blocker used in clinical practice for the management of angina pectoris. Since then, the use of β-blockers has diversified manifold and currently they are being used in a large variety of clinical conditions, ranging from cardiac diseases like hypertension, cardiac arrhythmias, myocardial infarction, to other indications like prophylaxis of migraine, anxiety, tremors, and thyrotoxicosis.