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<p>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 <b>PD-L1</b> 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/<b>PD-L1</b> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年8月27日

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  • Mahdieh Ameri Shah Reza,
  • Saina Najafi,
  • Masoumeh Kahfi,
  • Mustafa Safari,
  • Mohamad Mahjoor

摘要

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.