Bee venom in cancer: Cellular targets, preclinical evidence, and translational barriers

Objectives. Bee venom and its major peptide melittin can disrupt cell membranes and alter several cancer-related pathways, but systemic toxicity and the absence of clinical efficacy data limit translation. This review evaluated the cellular targets, preclinical evidence, delivery strategies, safety concerns, and requirements for clinical development. Methods. A structured narrative review searched Google Scholar, PubMed Central, relevant publisher platforms and Moldovan national repositories for English-language publications available through July 6, 2026. Priority was given to mechanistic studies, normal-cell comparators, animal tumor models, targeted-delivery investigations, and clinical evidence. Results. In preclinical models, melittin modifies tumor-cell membranes and growth-factor receptor organization; activates mitochondrial and death-receptor-mediated apoptosis; and affects phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K)/AKT/mTOR, mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor kappa B (NF-κB), autophagy, mitophagy, endoplasmic reticulum stress, and ferroptosis-related processes. Studies also report reduced cell-cycle progression, migration, invasion, and angiogenesis, together with improved responses to selected anticancer agents. Nanocarriers reduce direct erythrocyte exposure and improve tumor delivery in animal models, but clinical antitumor benefit has not been established. No approved melittin-based anticancer therapy was identified. Conclusions. Bee venom and melittin represent sources of bioactive compounds for anticancer drug development. However, their therapeutic potential remains preclinical, and current evidence does not support their use as alternatives to established cancer treatments. Further progress requires standardized preparations, pathway-specific validation, comparative safety studies, pharmacokinetic assessment, reproducible manufacturing, and controlled clinical trials.