Marine Natural Products for Cancer Therapy: From Molecular Mechanisms to Clinical Translation

Cancer continues to impose a major global health burden. Conventional therapies often show poor selectivity, off-target toxicity, and drug resistance, creating an urgent need for new agents. The marine environment covers roughly 71% of Earth’s surface and has fostered metabolites of unparalleled chemical diversity, making the ocean a vital source for anticancer drug discovery. This review critically examines the published literature on six representative marine-derived agents—cytarabine, trabectedin, eribulin, brentuximab vedotin, carrageenan, and Aspergillus fumigatus alkaloids. We compare their biological sources, anti-tumor spectra, molecular targets, and oncogenic pathways, and we analyze the structure—activity relationships and the total, semi-, and engineered synthesis routes that underpin their optimization. We also appraise the major barriers to clinical translation—sustainable supply, mechanistic ambiguity, and suboptimal druggability—alongside emerging solutions based on synthetic biology, multi-omics, artificial intelligence, and advanced formulation. Marine-derived agents therefore represent a chemically distinctive and mechanistically diverse reservoir for targeted cancer therapy. Realizing this potential will require structure—activity-guided optimization, secure synthetic or engineered supply, and biomarker-informed combination strategies that still await prospective validation.