Bioactive peptides in cancer and inflammation: Mechanisms, model systems and clinical translation
Bioactive peptides (BAPs), derived from both natural and synthetic sources, are increasingly recognized as multifunctional agents with potential roles in the management of cancer and inflammatory conditions, in addition to their well‐established antimicrobial activity. Their biological activity is critically governed by their sequence‐dependent physicochemical properties, including charge hydrophobicity, amphipathicity, and well‐defined three‐dimensional conformation, such as α‐helices, β‐sheets, and coils, which collectively determine target specificity, membrane interaction, and intracellular activity, ultimately determining therapeutic effectiveness and safety. Aside from in vitro models, animal models further validated their efficacy, enabling mechanistic insights and high‐throughput screening. In cancer models, BAPs induce anti‐cancer activity through various mechanisms such as membrane disruption, mitochondrial dysfunction, ROS generation, apoptosis, inhibition of invasion, migration, and angiogenesis across multiple cancer types, including breast cancer, particularly triple‐negative breast cancer, colorectal, lung and melanoma, highlighting BAPs broad antitumor properties. Concurrently, BAPs regulate the immune system through cytokine modulation, NF‐κB signalling suppression, reduced immune cell infiltration and macrophage polarization promotion. However, despite these advances, clinical translation remains limited due to poor stability, short half‐life, cytotoxicity, high production costs and optimized drug delivery systems. An integrated multidisciplinary approach with AI‐guided design places BAPs as promising precision medicine tools for specific, immunomodulatory, and personalized anticancer and anti‐inflammatory therapies.