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

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.

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.

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.

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.

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.