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.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Deciphering molecular pathways driving cancer invasion and metastasis: advances and therapeutic prospects.
转移是全球癌症相关死亡的主要原因。
转移是全球癌症相关死亡的主要原因。本叙述性综述通过专家引导的文献筛选,整合了近期在调控转移进展的分子回路方面的进展,涵盖上皮-间质转化(EMT)、器官趋向性、细胞外基质重塑、血管生成、缺氧诱导信号、肿瘤细胞迁移模式以及肿瘤-免疫相互作用。我们考察了干扰这些通路的治疗创新,包括EMT调节剂、基质金属蛋白酶抑制剂、VEGF/VEGFR靶向方案、缺氧激活前药,以及下一代免疫疗法如免疫检查点阻断和CAR-T 细胞。此外,我们讨论了已建立的基于纳米技术的递送系统、正在推进的多组学整合、不断发展的单细胞分析,以及新兴的CRISPR-Cas9基因编辑应用,作为改善转移检测、监测和治疗的工具。尽管取得了这些进展,转化障碍依然存在,特别是在瘤内异质性、适应性耐药和临床前模型保真度有限方面。应对这些挑战需要生物标志物引导的多靶点治疗组合、跨学科合作以及全球包容性临床试验。这些证据强调了整合策略的重要性,即同时靶向肿瘤内在可塑性和微环境支持,以改变转移性癌症的结局。
Metastasis is the primary cause of cancer-related mortality worldwide. This narrative review integrates recent advances in the molecular circuits orchestrating metastatic progression, encompassing epithelial-mesenchymal transition (EMT), organotropism, extracellular matrix remodeling, angiogenesis, hypoxia-inducible signaling, tumor-cell migration modes, and tumor-immune interactions through expert-guided literature selection. We examined therapeutic innovations that disrupt these pathways, including EMT modulators, matrix metalloproteinase inhibitors, VEGF/VEGFR-targeted regimens, hypoxia-activated prodrugs, and next-generation immunotherapies such as immune checkpoint blockade and chimeric antigen receptor T cells. Additionally, we discuss established nanotechnology-based delivery systems, advancing multi-omics integration, evolving single-cell analyses, and emerging CRISPR-Cas9 gene-editing applications as tools for improving metastasis detection, monitoring, and treatment. Despite this progress, translational obstacles persist, particularly regarding intratumoral heterogeneity, adaptive resistance, and limited preclinical model fidelity. Addressing these challenges requires biomarker-guided, multi-target therapeutic combinations, interdisciplinary collaboration, and globally inclusive clinical trials. This evidence underscores the importance of integrated strategies that simultaneously target intrinsic tumor plasticity and microenvironmental support to transform metastatic cancer outcomes.
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