Beta-glucans in oncology: revolutionizing treatment with immune power & tumor targeting.

Beta-glucans, naturally occurring polysaccharides derived from fungi, yeasts, cereals, and bacteria, have emerged as potent cancer therapeutics due to their multifaceted immunomodulatory, anti-inflammatory, and direct anti-tumor properties. These compounds engage pattern recognition receptors (PRRs) such as Dectin-1, Toll-like receptors (TLRs), and complement receptor 3 (CR3), activating macrophages, natural killer (NK) cells, and dendritic cells to enhance anti-tumor immunity. Beta-glucans suppress pro-inflammatory cytokines (e.g., TNF-α, IL-6) and tumor-promoting pathways like NF-κB, while modulating T-regulatory cells (Tregs) and downregulating PD-L1 to overcome immune evasion. They induce apoptosis via Bax/Bcl-2 regulation, arrest cell cycles at G1/S or G2/M phases, and inhibit angiogenesis by targeting VEGF and MMPs. Clinical trials (2023-2025) demonstrate significant survival benefits, such as improved overall survival (OS) in melanoma (hazard ratio [HR] 0.65, 95% CI 0.48-0.87) and lung cancer (HR 0.72, 95% CI 0.55-0.94), alongside reduced chemotherapy toxicity. Synergy with PD-1/PD-L1 inhibitors enhances immunotherapy efficacy, particularly in immunogenic tumors. Advanced nano-delivery systems, including micelles and exosomes, improve bioavailability and tumor targeting. However, challenges like variable bioavailability, dosing inconsistencies, side effects (e.g., gastrointestinal discomfort in 10-15% of patients, allergic reactions in 2-5%), and conflicting efficacy data across tumor types necessitate further research. This review consolidates beta-glucan mechanisms, clinical evidence, delivery innovations, and challenges, positioning them as promising adjuncts in precision oncology.