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Review highlights the role of natural compounds in modifying the tumor microenvironment and their therapeutic potential.
Natural products derived from plants, fungi, and marine organisms have emerged as crucial modulators of the tumor microenvironment (TME), exhibiting diverse anticancer properties. This review highlights the molecular mechanisms and therapeutic relevance of polyphenols, flavonoids, alkaloids, triterpenoids, sulfur-containing compounds, carotenoids, and microbial-derived agents in targeting key hallmarks of cancer. Compounds such as curcumin, resveratrol, epigallocatechin-3-gallate (EGCG), quercetin, berberine, sulforaphane, and β-glucans exert multi-targeted effects by modulating signaling pathways including PI3K/Akt, nuclear factor kappa B, STAT3, and activated protein kinase (MAPK). These natural agents influence the TME by inducing apoptosis, arresting the cell cycle, inhibiting angiogenesis and metastasis, and enhancing immune responses. Furthermore, semisynthetic derivatives such as topotecan, irinotecan, and etoposide underscore the translational potential of natural scaffolds in clinical oncology. Their ability to overcome chemoresistance and synergize with conventional therapies offers promising avenues for integrative cancer treatment. Overall, this review provides a comprehensive overview of how herbal and marine bioactives can reshape the TME, supporting their continued exploration as adjuvants or stand-alone agents in cancer prevention and therapy.
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Krishnasamy et al. (2025) studied this question.
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