From the lab to the clinic: the journey of dermaseptins toward cancer treatment

Cancer remains a global health burden driven by high incidence, therapeutic resistance, and toxicity of current treatments. Dermaseptins, amphibian-derived peptides, have attracted attention as anticancer agents due to selective cytotoxicity and membrane-targeting activity. This systematic review critically evaluates the anticancer potential of dermaseptins across experimental cancer models. A PRISMA-guided, PROSPERO-registered search of PubMed, Web of Science, and Scopus identified 21 eligible studies, mainly in vitro, with limited in vivo validation. Dermaseptin variants including DRS-B2, PH, and SS1 were analyzed for potency, mechanisms of action, and selectivity. Dermaseptins showed robust activity against lung, prostate, and breast cancer cell lines, with IC₅。 values predominantly in the low micromolar range. Antitumor effects were largely mediated by membrane disruption and apoptosis, with minimal toxicity toward normal cells. Although direct comparisons with standard chemotherapeutics are scarce, dermaseptins emerge as versatile anticancer candidates with translational clinical promise. Cancer treatment remains challenged by drug resistance and adverse side effects. This systematic review highlights dermaseptins, amphibian-derived peptides, as potent and selective anticancer agents with minimal toxicity to normal cells. By integrating current preclinical findings, the study underscores dermaseptins as promising candidates for safer cancer therapies and outlines key research gaps that must be addressed to support their clinical translation.