Marine Traditional Chinese Materia Medica in Oncology: Mechanisms, Multi-Omics Insights, and Translational Prospects

Background/Objectives: Marine traditional Chinese materia medica (TCMM)—including sulfated polysaccharides (for example, fucoidan), triterpenoid saponins (for example, frondoside A), bioactive peptides, and nacre/pearl matrices—occupies a chemical space distinct from terrestrial remedies. Growing oncologic interest requires a clear link between traditional efficacy claims and modern mechanistic and translational standards. A growing number of studies have reported antitumor activities of marine TCMMs in vitro, in vivo, and in early clinical settings. This review synthesizes these anticancer data within a framework spanning mechanism → multi-omics → quality (critical quality attributes, CQAs) → clinical, and uses fucoidan, frondoside A, and nacre as anchor exemplars for vertical translation along this continuum. Methods: We performed a narrative, mechanism-anchored review of marine TCMMs in oncology, focusing on four major chemotypes: sulfated polysaccharides, triterpenoid saponins, peptides/matrix proteins, and mineral–organic composites. Evidence extraction covered active-constituent characterization by LC/HPSEC-MALS/MS/NMR, high-content phenotypic screening (HCS), network pharmacology and in-silico modelling, and in-vivo efficacy studies with pharmacokinetics/pharmacodynamics (PK/PD) and bioanalytics. We then organized multi-omics readouts—transcriptomics, proteomics/phosphoproteomics, metabolomics/lipidomics, epigenomics/post-translational modifications, and immunomics/tumor microenvironment profiling—into mechanism-oriented “minimal biomarker sets” that link CQAs, exposure, pathway engagement, and preclinical or early clinical endpoints. Results: Marine TCMMs converged on four core anticancer mechanisms. First, triterpenoid saponins such as frondoside A promoted mitochondrial p53–caspase apoptosis, restrained pro-survival autophagy, and in some settings also pushed cells toward ferroptosis, with key nodes including SLC7A11, GPX4, ACSL4, FSP1, FDX1, and redox-sensitive actin networks. Second, several agents reshaped the tumor immune microenvironment (TIME): fucoidan increased natural killer cell cytotoxicity in humans, whereas trabectedin and lurbinectedin depleted monocytes and tumor-associated macrophages and restored T-cell activity, converging on STAT3, NF-κB, and prostaglandin EP signaling as shared immune hubs. Third, many studies reported reduced HIF-1α and VEGF signaling, lower matrix metalloproteinase expression, and inhibition of epithelial–mesenchymal transition, linking regulated cell death, immunity, and metabolism through the angiogenesis–invasion axis. Finally, multi-omics datasets supported compact biomarker panels that can track pathway engagement, capture exposure–response relationships, and guide mechanism-based trial design. Conclusions: Marine TCMMs couple polypharmacology with omics tractability. Convergent evidence supports mechanism-anchored development using defined CQAs, exposure measurements, and biomarker endpoints, particularly along ferroptosis and tumor-microenvironment axes and in hypoxia/angiogenesis–invasion biology. Key gaps include material heterogeneity, incomplete exposure–response characterization, and a limited number of randomized clinical trials with standardized products. Addressing these gaps through harmonized analytics, transparent reporting, and cautious, biomarker-driven trials may enable reliable integration of marine TCMMs into precision oncology.