Researchers have shown that the use of β-adrenoceptor antagonists (β-blockers) for 1 year or more is associated with a decreased risk of progression of thick malignant melanoma.
Researchers have shown that the use of β-adrenoceptor antagonists (β-blockers) for 1 year or more is associated with a decreased risk of progression of thick malignant melanoma. The research team, from the University of Florence, suggest that the results warrant a large randomized clinical trial and larger epidemiological studies. The study is published in the Archives of Internal Medicine (doi:10.1001/archinternmed.2011.131).
B1-selective β-blockers; source: Wikimedia Commons, user Yikrazul
Based on pre-clinical evidence, which has shown that β-blockers both inhibit tumor and metastasis progression in animal models of melanoma, the authors hypothesized that β-blocker usage for concomitant diseases is associated with a reduced risk of progression of thick malignant melanoma. 30 patients taking β-blockers for at least 1 year and 91 patients not treated with β-blockers who had been diagnosed with thick melanoma were followed up for a median of 2.5 years.
While tumor progression was observed in 34.1% of the untreated subgroup, only 3.3% of the treated subgroup exhibited tumor progression. The study showed a 36% reduced risk reduction (P = .002) for every year of β-blocker use. Interestingly, none of the 30 β-blocker-treated patients died during the study follow-up. Twenty-four of the patients in the "not treated with β-blockers group" died.
In an October 10, 2011 commentary in the journal, Dr. Marko Lens of King’s College, London, UK, highlights the result and stresses the need to further explore β-blockers as melanoma therapy due to the “limited evidence” that suggests that β-blockers may reduce tumor recurrence in other malignant diseases.
Dr.Lens postulates that the presence of β-adrenoceptors in both primary and metastatic melanoma may be required for the action of β-blockers in melanoma patients. How β-blockers actually affect melanoma progression is a topic that needs to be addressed. Because melanoma is highly resistant to cytotoxic agents of therapy due to deactivated apoptotic pathways, β-blockers may be inducing apoptotic activity in these tumors. Dr. Lens believes that use of β-blockers in delaying melanoma progression merits a larger epidemiological study and randomized clinical trials.
In a reply to Dr. Len’s comment, the authors of the research state that their working hypothesis is that the benefit of β-blockers in melanoma is likely because β-adrenoceptors promote angiogenesis. This idea is supported by both basic and clinical evidence. It is also a possibility, they note, that there is a contribution from the inhibition of β-blockers of additional pathways, such as the 2 metalloproteinases, MMP-2 and MMP-9, which are involved in angiogenesis. The researchers also note that a reduced risk of relapse with triple-negative breast cancer has been associated with selective β-receptor antagonists. Randomized trials will help to provide clarity on the role of β-blockers in melanoma as well as other cancers.