Didemnins as marine-derived anticancer agents: mechanistic insights and clinical potential.

Abstract

Didemnins, a class of cyclic depsipeptides derived from marine organisms exhibit notable anticancer properties. Among them, Didemnin B has been extensively researched for its strong antitumor activity and progression to clinical trials. Nonetheless, its clinical application has been impeded by challenges like poor bioavailability and dose-limiting toxicity. This review aims to provide a comprehensive analysis of the anticancer mechanisms of Didemnins, particularly Didemnin B, by examining studies that investigate their anticancer properties, mechanisms of action, pharmacokinetics, and clinical outcomes, while exploring their potential as therapeutic agents in cancer treatment. A comprehensive review of the literature was conducted using scientific databases, including PubMed, Google Scholar and ScienceDirect. Didemnin B has been shown to exert its anticancer effects primarily through the inhibition of protein synthesis, induction of apoptosis, and disruption of cell-cycle progression. Despite promising preclinical results, clinical trials have revealed substantial toxicity, particularly neuromuscular and hepatic, which significantly constrains its therapeutic potential. Recent progress in developing semisynthetic derivatives, including Dehydrodidemnin B (Plitidepsin, Aplidin), have led to improved efficacy and reduced toxicity. Didemnins, especially Didemnin B, hold promise as anticancer agents. However, future research should focus on optimizing delivery methods, reducing toxicity, and exploring combination therapies to enhance their therapeutic potential in oncology.