决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
英文原题:Clinical and Therapeutic Relevance of B7-H3 in Sarcomas: Molecular Insights from a Systematic Review.
Clinical and Therapeutic Relevance of B7-H3 in Sarcomas: Molecular Insights from a Systematic Review.
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肉瘤是一组异质性间叶源性恶性肿瘤,具有显著的形态学和分子多样性。尽管手术和全身治疗取得了进展,但预后仍然不佳,这凸显了对新型生物标志物和靶向治疗的需求。我们系统评估了肉瘤中 B7-H3 的状态。共纳入 46 项研究(25 项临床前研究、13 项临床研究和 8 项混合研究),其中大多数聚焦于骨肉瘤、横纹肌肉瘤和尤文肉瘤。B7-H3 的表达在不同肉瘤亚型之间以及根据检测和评分方法的不同而差异很大。现有证据提示 B7-H3 参与致癌转录程序、miR-124 下调、基质金属蛋白酶介导的脱落,以及包括 PI3K-AKT-mTOR、MAPK、Wnt/β-catenin 和上皮-间质转化在内的信号通路。
Sarcomas are a heterogeneous group of mesenchymal malignancies characterized by substantial morphological and molecular diversity. Despite advances in surgery and systemic therapies, outcomes remain poor, underscoring the need for novel biomarkers and targeted therapies.
We systematically assessed B7-H3 status in sarcomas. Forty-six studies were included (25 preclinical, 13 clinical, and eight mixed studies), most of which focused on osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma. B7-H3 expression varied considerably across sarcoma subtypes and according to detection and scoring methods. The available evidence implicated B7-H3 in oncogenic transcriptional programs, miR-124 downregulation, matrix metalloproteinase-mediated shedding, and signaling pathways including PI3K-AKT-mTOR, MAPK, Wnt/β-catenin, and epithelial-mesenchymal transition.
Emerging therapeutic strategies targeting B7-H3 included CAR T-cell therapies, antibody-drug conjugates, Fc-optimized antibodies, radiolabeled antibodies, and fluorescence-guided surgery.
In clinical evidence, B7-H3 expression showed potential associations with disease progression and selected survival outcomes; however, findings were limited by heterogeneous methodologies and relatively sparse clinical data. B7-H3 represents a promising biomarker and therapeutic target in sarcomas, with substantial preclinical evidence supporting its biological and therapeutic relevance.
However, standardized approaches to B7-H3 detection and scoring, together with well-designed prospective clinical studies, are needed to establish its prognostic and predictive value and determine the clinical efficacy of B7-H3-directed therapies.
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