CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.
Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.
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癌症干细胞(CSC)通过独特的膜生物学、糖基化模式和代谢适应,推动肿瘤进展、治疗耐药和转移。CSC 具有独特的糖萼特征,富含透明质酸、硫酸乙酰肝素和唾液酸化聚糖,有助于免疫逃逸、黏附和存活。Wnt/β-catenin、Hedgehog、Notch、JAK/STAT、TGF/SMAD 和 PI3K/AKT/mTOR 等关键信号通路调节 CSC 干性和治疗耐药。新兴生物标志物(CD44、CD133、ALDH1、EpCAM)和靶向疗法(CAR-T、miRNA 调节、脂质代谢抑制剂)在破坏 CSC 韧性方面显示潜力。单细胞组学、CRISPR 筛选和患者来源类器官(PDO)等进展,改善了 CSC 表征并拓展精准医疗应用。但类器官培养标准化、肿瘤微环境重建及克服 CSC 可塑性仍具挑战。将 CSC 靶向策略与传统疗法结合,可能通过清除耐药细胞群并预防复发来改善临床结局。本综述强调,需要创新联合疗法以清除 CSC、改善临床结局,同时解决生物标志物验证、治疗耐药和转化应用方面的挑战。
Cancer stem cells (CSCs) drive tumor progression, therapy resistance, and metastasis through unique membrane biology, glycosylation patterns, and metabolic adaptations. CSCs exhibit a distinct glycocalyx profile enriched in hyaluronan, heparan sulfate, and sialylated glycans, facilitating immune evasion, adhesion, and survival.
Key signaling pathways-Wnt/ -catenin, Hedgehog, Notch, JAK/STAT, TGF/SMAD, and PI3K/AKT/mTOR-regulate CSC stemness and therapeutic resistance. Emerging biomarkers (CD44, CD133, ALDH1, EpCAM) and targeted therapies (CAR-T cells, miRNA modulation, lipid metabolism inhibitors) show promise in disrupting CSC resilience. Advances in single-cell omics, CRISPR screening, and patient-derived organoids (PDOs) enhance CSC characterization and precision medicine applications.
However, challenges remain in standardizing organoid cultures, replicating tumor microenvironments, and overcoming CSC plasticity. Integrating CSC-targeted strategies with conventional therapies may improve clinical outcomes by eradicating therapy-resistant populations and preventing relapse. This review underscores the need for innovative combination therapies to eradicate CSCs and improve clinical outcomes, while addressing challenges in biomarker validation, therapeutic resistance, and translational applications.
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