Abstract
• Marine mollusks yield diverse anticancer compounds with selective cytotoxicity. • Novel epigenetic modulators target DNMTs and HDACs for cancer therapy. • Kahalalide F in trials; liposomal delivery enhances clinical potential. Marine natural products have long provided scaffolds for cancer drug discovery, with several mollusk-derived compounds such as dolastatins and Kahalalide F (C6) progressing into clinical evaluation. Marine heterobranch mollusks, in particular, produce or sequester structurally diverse metabolites that have attracted interest for their potent and selective anticancer activities. This comprehensive review highlights the diverse chemical classes of mollusk-derived metabolites, including terpenoids, alkaloids, and peptides, and their mechanisms of action, such as cytoskeletal disruption, DNA damage induction, and oxidative stress-mediated apoptosis. Notably, some compounds are selectively toxic to cancer cells by exploiting elevated reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. Emerging evidence indicates that methylthioadenosine analogs and polyunsaturated fatty acids (PUFAs (C12)) can modulate DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), suggesting new avenues for epigenetic cancer therapy. Despite challenges in sustainable sourcing, advancements in synthesis and drug delivery systems, including liposomal formulations, enhance their clinical translatability. This review underscores the potential of marine mollusk-derived compounds as innovative anticancer agents, emphasizing their unique mechanisms and therapeutic promise.