Frontiers in Medicine 2026 Comprehensive Review on Antimicrobial Peptides (AMPs) as Cancer Treatments and Vaccines Synthesizes the Growing Body of Preclinical and Early-Clinical Evidence for Cationic Amphipathic Peptides That Selectively Target the Negatively Charged Phospholipid Outer Leaflets of Malignant Cell Membranes to Produce Selective Cytotoxicity via Membrane Disruption Plus Intracellular Actions Including Inhibition of DNA Replication and Protein Synthesis, Induction of Mitochondrial Dysfunction, and Suppression of Tumor Angiogenesis; The Review Extends the AMP-Anticancer Research Trajectory Anchored by the August 7 Nature aMPC16-CA50 Membranolytic Peptide Study and Recent Frog-Skin AMP (Dermaseptins, Temporins, Brevinins) Coverage; Challenges Remaining Include High Toxicity at Effective Anticancer Doses, Poor Systemic Stability, Limited Cellular Penetration, and Costly Synthesis but the Mechanism Diversity Across Natural-Origin, Synthetic, and AI-Designed AMPs Continues to Expand
Frontiers in Medicine 2026 comprehensive review on antimicrobial peptides (AMPs) as cancer treatments and vaccines synthesizes the growing body of preclinical and early-clinical evidence. Mechanism synthesis: AMPs are cationic (positively charged) amphipathic (both water-loving and lipid-loving) peptides that selectively interact with the negatively charged phospholipid outer leaflets of malignant cell membranes (produced by higher phosphatidylserine externalization in cancer cells compared to normal cells). This selectivity produces cytotoxicity through membrane disruption, followed by intracellular actions including inhibition of DNA replication and protein synthesis, induction of mitochondrial dysfunction (opening the mitochondrial permeability transition pore to release cytochrome c and trigger apoptosis), and suppression of tumor angiogenesis (reducing tumor vascular supply). The review extends the AMP-anticancer research trajectory anchored by the August 7, 2026 Nature aMPC16-CA50 synthetic acid-responsive membranolytic peptide study and recent MDPI Antibiotics coverage of frog-skin AMP families (dermaseptins from Phyllomedusa frogs, temporins from Rana temporaria, brevinins from Rana and Sylvirana). Ongoing translation challenges include high systemic toxicity at effective anticancer doses (requiring tumor-selective delivery), poor systemic stability (peptidase degradation in blood), limited cellular penetration (large hydrophilic molecules), and costly synthesis (multi-step solid-phase peptide synthesis at gram-scale). Mechanism diversity across natural-origin, synthetic (using natural templates), and AI-designed AMPs (using machine learning to design novel sequences with optimized properties) continues to expand the therapeutic pipeline.