Recent advances in the molecular interactions of anti-cancer peptides with cellular targets.

Anti-cancer peptides (ACPs) selectively kill tumor cells through membrane disruption, intracellular target engagement, and immune activation. Recent structural and computational advances have clarified structure-activity relationships, enabling rational engineering via cyclisation, D-amino acid incorporation, and nanoparticle delivery. This review integrates current understanding of ACP-cellular interactions, with emphasis on clinical-stage agents and the integration of artificial intelligence in peptide design. Key barriers like proteolytic instability, tumor penetration, and acquired resistance are evaluated alongside emerging solutions, including stapled peptides, tumor-activatable linkers, and combination regimens. With more than 80 candidates in trials and the first approvals anticipated within 3-5 years, ACPs are positioned to complement personalized oncology.