Key result
Beta-blockers reduce preclinical melanoma progression but lack clear translational validity.
Why the study?
Antihypertensive medications have attracted attention for potential antitumor effects, but evidence on repositioning them for melanoma management had not been systematically mapped and critically appraised.
Systematic Review (n=37)
Antihypertensive agents, particularly β-blockers, show promising but heterogeneous preclinical signals in melanoma, requiring standardized and rigorous studies before clinical investigation.
Current evidence does not support antihypertensive repurposing for melanoma; leaves open whether standardized preclinical models can achieve translational validity.
Background/Objectives: Melanoma remains one of the most aggressive skin cancers worldwide, with rising incidence and persistent therapeutic challenges, particularly in advanced diseases. Drug repositioning has emerged as a cost- and time-efficient strategy for identifying adjunctive treatments, and antihypertensive medications have attracted attention for their potential off-target antitumor and immunomodulatory effects. This scoping review aimed to map and critically appraise the evidence on the repositioning of antihypertensive drugs for melanoma management. Methods: The review followed the JBI methodology, and the results were reported in accordance with the PRISMA-ScR guidelines. Searches were conducted in July 2025 and updated in May 2026 in PubMed, Scopus, and Web of Science. For Methodological Quality and Risk-of-bias assessment, the SYRCLE Risk of Bias tool was employed for animal studies. Results: This review included 37 studies. β-Blockers, particularly propranolol, were the most frequently investigated agents (n = 21). Several studies reported antiproliferative, pro-apoptotic, antiangiogenic, and immunomodulatory effects; however, these findings were not uniform. Absent direct antiproliferative effects, biphasic dose responses, lack of angiogenic effects, and outcomes dependent on drug concentration, treatment schedule, and experimental model were also reported. Agents targeting the renin–angiotensin system and calcium channels similarly produced heterogeneous and context-dependent findings. The animal studies frequently presented high or unclear risk of bias, particularly because of incomplete reporting of randomization, allocation concealment, and blinding. No formal methodological quality assessment was performed for the in vitro studies. Conclusions: Antihypertensive agents, particularly β-blockers, show promising but heterogeneous preclinical signals in melanoma. However, the available evidence is not sufficient to establish reproducible efficacy or translational validity. Standardized and methodologically rigorous preclinical studies are required before these agents can be considered for clinical investigation as adjunctive melanoma therapies.
No takes yet. Share an insight, caveat, or question.
Mieres et al. (2026) conducted a systematic review in Melanoma (n=37). Antihypertensive drugs (e.g., beta-blockers) vs. Control was evaluated on Melanoma progression or antitumor activity. Antihypertensive agents, particularly beta-blockers, show promising but heterogeneous preclinical signals in reducing melanoma progression, though current evidence lacks translational validity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: