Venom-Derived Peptides in Breast Cancer: Pharmacological Mechanisms and Medicinal Chemistry-Guided Translational Development.

Breast cancer remains the most prevalent malignancy among women worldwide and continues to present major therapeutic challenges, including drug resistance, systemic toxicity, and limited long-term efficacy despite advances in multimodal treatment strategies. These limitations have intensified interest in venom-derived peptides as structurally diverse bioactive scaffolds with anticancer potential. This review evaluates venom-derived peptides in breast cancer from a medicinal chemistry and translational drug development perspective. A structured narrative synthesis of the literature was conducted, covering preclinical and early translational studies of peptides derived from snakes, spiders, scorpions, and bees, with emphasis on structure-function relationships, mechanisms of action, and optimization strategies. Unlike previous reviews that primarily focus on individual venom sources, this work integrates mechanistic pharmacology with peptide engineering and translational constraints to provide a unified drug-development framework across breast cancer subtypes. Venom-derived peptides exert anticancer effects through ion channel modulation, apoptosis induction, cell cycle arrest, angiogenesis inhibition, membrane disruption, and immune modulation, with reported selectivity toward malignant cells in triple-negative, HER2-positive, and hormone receptor-positive models. Despite encouraging preclinical evidence, clinical translation is limited by instability, immunogenicity, poor pharmacokinetics, delivery barriers, and manufacturing challenges. Emerging advances in peptide engineering, nanodelivery systems, and artificial intelligence-assisted design offer promising strategies to improve pharmacological performance and drug-like properties. Overall, this review provides a medicinal chemistry-guided framework that identifies the key steps and remaining challenges required to support the future development of venom-derived peptides as anticancer lead scaffolds for breast cancer.