Melittin in Aggressive Breast Cancer Therapy: Mechanisms, Delivery Systems, and Clinical Potential.

INTRODUCTION: Aggressive breast cancer subtypes, including Triple-Negative Breast Cancer (TNBC) and HER2-positive tumours, remain clinically challenging due to poor prognosis, high therapeutic resistance, and limited targeted treatment options, highlighting the urgent need for novel and more effective therapeutic strategies. METHODS: This study presents a narrative review of preclinical and mechanistic studies evaluating the anticancer potential of melittin, a bioactive peptide derived from bee venom, with emphasis on molecular mechanisms and advancements in targeted delivery systems. RESULTS: Preclinical studies have demonstrated that melittin has potent anticancer activity through membrane disruption, induction of apoptosis, and inhibition of EGFR/HER2 signalling pathways. Reported IC₅₀ values range from approximately 0.8-2.0 μM in aggressive breast cancer cell lines, whereas targeted delivery systems, such as nanoparticles and liposomes, reduce haemolysis from ~40-60% to <10%, significantly improving therapeutic selectivity. Additionally, melittin has enhanced chemosensitivity and modulates tumour-associated immune responses, including PD-L1 downregulation. DISCUSSION: The multi-modal mechanisms of melittin, combined with advances in targeted delivery platforms, position it as a promising candidate for overcoming therapeutic resistance and toxicity limitations in aggressive breast cancer. CONCLUSION: Melittin-based therapies, particularly when integrated with advanced delivery systems, represent a promising translational strategy for aggressive breast cancer. Further research should prioritise well-designed clinical trials, optimisation of dosing strategies, and validation of targeted delivery platforms to enable safe and effective clinical application.