Natural polysaccharides as multifunctional anti-cancer agents: structure-activity relationships, mechanisms of action, and therapeutic potential

Cancer remains a formidable global health challenge, characterized by alarmingly high incidence and mortality rates. Traditional clinical therapies are often accompanied by obvious toxicity and side effects, highlighting the urgent need to develop safer and more effective therapeutic alternatives. In recent years, polysaccharides have emerged as promising candidates for anti-tumor drugs due to their wide sources, high biocompatibility and low toxicity. This review summarizes recent advances in anti-tumor effects of polysaccharides, covering their underlying mechanisms, key signaling pathways and selective toxicity characteristics. Polysaccharides exert synergistic anti-cancer effects through multi-target, multi-pathway mechanisms, including the induction of immune cell polarization and tumor cell apoptosis, inhibition of tumor cell migration and angiogenesis, and modulation of key signaling pathways such as P53, NF-κB, and Wnt/β-catenin. Among these, polysaccharides with specific monosaccharide compositions, optimal molecular weights, β-glycosidic linkages, triple-helix conformations, or those that are chemically modified, exhibit enhanced biological and anti-tumor activities. Future efforts should focus on elucidating structure-activity relationships, developing targeted delivery systems to improve bioavailability and tumor specificity, and advancing large-scale, multi-center, long-term clinical trials to support the development of safe and effective polysaccharide-based anti-cancer therapeutics.