Melittin in AllergoOncology: From Honey Bee Venom to Anti-Cancer Therapeutic Innovation—An EAACI Position Paper

Honey bee venom (HBV) represents a unique interface between allergy and oncology, exemplifying how allergen-derived molecules can be repurposed as anti-cancer agents. Melittin, the principal component of HBV, accounts for 40%–50% of its dry weight and is responsible for most of its biological activity. Beyond its well-established role as a potent allergen and mast cell activator, melittin displays broad anti-tumour properties across multiple cancer models. Preclinical evidence demonstrates that melittin induces cancer cell death through membrane disruption, mitochondrial and death receptor–mediated apoptosis, ferroptosis, and inhibition of key oncogenic pathways, including PI3K/Akt/mTOR, NF-κB, and HIF-1α/VEGF signalling. Additional effects include suppression of angiogenesis, epithelial–mesenchymal transition, invasion, and metastatic dissemination, as well as modulation of the tumour immune microenvironment. However, the clinical translation of melittin is limited by its intrinsic haemolytic activity, systemic toxicity, and high allergenic potential. Advances in nanotechnology, targeted delivery systems, and venom-inspired peptide engineering are addressing these barriers, enabling tumour-selective delivery while reducing off-target effects. This EAACI Task Force Position Paper integrates current evidence on melittin within the emerging field of AllergoOncology. It highlights its dual relevance for allergists and oncologists and outlines the translational challenges to be overcome and opportunities to enable safe clinical application.