Introduction
Marine ecosystems are a vast reservoir of chemically diverse compounds with potent biological activities. From sponges and algae to tunicates and microorganisms, the oceans host molecules that can interact with cancer-related pathways in unique ways. As researchers uncover how these marine-derived compounds work, they open new avenues for targeted therapies, combination strategies, and personalized oncology. This article reviews the mechanisms by which marine-derived compounds exert anti-cancer effects and discusses their therapeutic implications and challenges for future clinical translation.
Marine sources and representative compounds
The chemical diversity of marine life offers a broad palette of anti-cancer candidates. Notable sources include marine sponges, soft corals, macroalgae, tunicates, and marine microorganisms. Representative classes of compounds include alkaloids, polyketides, terpenoids, and peptides. Some molecules display single-agent activity, while others serve as scaffolds for synthetic modification to improve potency, selectivity, and pharmacokinetic properties. The structural novelty of many marine-derived compounds helps overcome resistance mechanisms that limit conventional chemotherapies.
Mechanisms of anti-cancer action
Inducing apoptosis and cell-cycle arrest
A common mechanism involves triggering programmed cell death in cancer cells. Marine-derived agents can activate intrinsic or extrinsic apoptotic pathways, modulate BCL-2 family proteins, and influence caspase cascades. Additionally, several compounds cause cell-cycle arrest at G1, S, or G2/M phases, inhibiting proliferation and sensitizing tumors to other therapies.
Anti-angiogenesis and microenvironment modulation
To starve tumors of blood supply, many marine compounds hinder angiogenesis by targeting VEGF signaling, matrix metalloproteinases, or endothelial cell function. By altering the tumor microenvironment—reducing hypoxia, remodeling extracellular matrix, and modulating immune cell infiltration—these agents can enhance anti-tumor efficacy and overcome resistance associated with angiogenic pathways.
Immunomodulation and combination potential
Emerging evidence shows that certain marine-derived molecules can boost anti-tumor immunity, for example by activating dendritic cells, enhancing cytotoxic T cell responses, or reshaping macrophage phenotypes. This immunomodulatory activity makes them attractive partners in combination regimens with immune checkpoint inhibitors, radiotherapy, or conventional chemotherapies, aiming to achieve synergistic tumor control with manageable toxicity.
Targeting tumor metabolism and signaling
Some marine compounds interfere with cancer cell metabolism, inhibiting pathways such as glycolysis or mitochondrial function, which are often reprogrammed in tumors. Others directly target dysregulated signaling networks (e.g., PI3K/AKT/mTOR, MAPK) that drive proliferation, survival, and metastasis. The ability to hit multiple nodes can reduce the likelihood of resistance development compared with single-target therapies.
Therapeutic implications and translational considerations
The therapeutic promise of marine-derived compounds lies in their novelty, potency, and potential to address unmet clinical needs. However, translating these agents into safe, effective drugs requires navigating several challenges:
- Supply and sustainability: Many marine compounds are found in scarce quantities; scalable synthesis or aquaculture approaches are essential to ensure consistent supply for clinical development.
- Drug-likeness and pharmacokinetics: Natural products often face issues with solubility, stability, and bioavailability. Medicinal chemistry and formulation strategies are used to optimize pharmacokinetic profiles while preserving activity.
- Selectivity and toxicity: Achieving tumor-specific effects with acceptable safety is critical. Careful profiling in preclinical models helps distinguish therapeutic windows and informs dosing strategies.
- Clinical trial design: Given heterogeneity in cancer biology, identifying responsive patient subgroups based on biomarkers will be key to demonstrating clinical benefit in trials.
Future directions
Advances in genomics, metabolomics, and high-throughput screening are accelerating the discovery of marine-derived anti-cancer agents. Integrated approaches—combining marine-derived compounds with immunotherapies, targeted inhibitors, or standard chemotherapies—hold promise for enhanced efficacy and reduced resistance. Collaborative efforts among marine biologists, chemists, pharmacologists, and clinicians will be essential to translate exciting preclinical findings into approved therapies that benefit patients.
