RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:A pioneer review on lactoferrin as versatile macromolecular ligand for targeting cancer: recent advances.
A pioneer review on lactoferrin as versatile macromolecular ligand for targeting cancer: recent advances.
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本综述批判性评估了乳铁蛋白——一种铁螯合糖蛋白——作为大分子配体在精准癌症治疗中的新兴作用。乳铁蛋白具有强效的抗肿瘤、抗炎和免疫调节特性,并通过与转铁蛋白和LDL受体相关蛋白的高亲和力结合靶向癌细胞,增强选择性并最大限度减少脱靶毒性。它调节PI3K/Akt和MAPK等关键致癌通路,以抑制肿瘤生长和转移。脂质体和聚合物纳米颗粒等纳米制剂可改善药代动力学,实现靶向药物递送,并增强治疗效果。乳铁蛋白穿越生物屏障的能力,包括通过受体介导的转胞吞作用穿越血脑屏障,为治疗胶质母细胞瘤等难治性癌症带来了希望。此外,它通过激活NK细胞并将巨噬细胞极化为M1表型来增强抗肿瘤免疫。重要的是,乳铁蛋白通过调节P-糖蛋白等外排泵,有助于克服多药耐药。本综述将分子层面的见解与临床前和临床证据相结合,强调乳铁蛋白通过先进纳米制剂和协同免疫调节机制在精准肿瘤学中的变革性潜力。
This review critically evaluates the emerging role of lactoferrin, an iron-chelating glycoprotein, as a macromolecular ligand in precision cancer therapy. Lactoferrin exhibits potent anti-tumour, anti-inflammatory, and immunomodulatory properties and targets cancer cells via high-affinity binding to transferrin and LDL receptor-related proteins, enhancing selectivity and minimizing off-target toxicity.
It modulates key oncogenic pathways such as PI3K/Akt and MAPK to suppress tumour growth and metastasis. Nanoformulations-like liposomes and polymeric nanoparticles-improve pharmacokinetics, enable targeted drug delivery, and enhance therapeutic efficacy. Lactoferrin's ability to cross biological barriers, including the blood-brain barrier via receptor-mediated transcytosis, offers promise for treating difficult cancers such as glioblastoma.
Additionally, it enhances anti-tumour immunity by activating NK cells and polarizing macrophages to the M1 phenotype.
Importantly, lactoferrin helps overcome multidrug resistance by modulating efflux pumps like P-glycoprotein. Integrating molecular insights with preclinical and clinical evidence, this review underscores lactoferrin's transformative potential in precision oncology through advanced nanoformulations and synergistic immunomodulatory mechanisms.
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