CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:GRP78 in Glioma Progression and Therapy: Implications for Targeted Approaches.
GRP78 in Glioma Progression and Therapy: Implications for Targeted Approaches.
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胶质瘤是最常见的原发性恶性脑肿瘤,占脑癌相关死亡的大多数。鉴于传统疗法疗效有限,人们开发了新的分子靶向疗法以改善预后并尽量减少毒性。葡萄糖调节蛋白78(GRP78)是一种主要定位于内质网(ER)的分子伴侣,因其在胶质瘤进展和对传统疗法耐药中的作用而受到越来越多的关注。GRP78在胶质瘤中过表达,通过维持细胞稳态和调控多条信号通路来支持肿瘤生长、存活和治疗耐药。其异常表达与更高的肿瘤分级和更差的患者预后相关。除了细胞内功能外,GRP78在细胞表面的存在及其在肿瘤微环境中的作用凸显了其作为治疗靶点的潜力。近期研究探索了靶向GRP78的创新策略,包括小分子抑制剂、单克隆抗体和嵌合抗原受体(CAR)T细胞疗法,在胶质瘤治疗中显示出显著潜力。本综述探讨了GRP78的生物学特征、其在胶质瘤病理生理中的作用,以及GRP78靶向治疗作为克服治疗耐药和改善临床结局的新策略的潜力。GRP78靶向治疗,无论是单独使用还是与传统治疗联合,都可能成为未来胶质瘤治疗的一种新颖且有吸引力的策略。
Glioma is the most common primary malignant brain tumor, accounting for the majority of brain cancer-related deaths. Considering the limited efficacy of conventional therapies, novel molecular targeted therapies have been developed to improve outcomes and minimize toxicity. Glucose-regulated protein 78 (GRP78), a molecular chaperone primarily localized in the endoplasmic reticulum (ER), has received increasing attention for its role in glioma progression and resistance to conventional therapies. Overexpressed in gliomas, GRP78 supports tumor growth, survival, and therapeutic resistance by maintaining cellular homeostasis and regulating multiple signaling pathways. Its aberrant expression correlates with higher tumor grades and poorer patient prognosis.
Beyond its intracellular functions, GRP78's presence on the cell surface and its role in the tumor microenvironment underscore its potential as a therapeutic target. Recent studies have explored innovative strategies to target GRP78, including small molecule inhibitors, monoclonal antibodies, and chimeric antigen receptor (CAR) T cell therapy, showing significant potential in glioma treatment.
This review explores the biological characteristics of GRP78, its role in glioma pathophysiology, and the potential of GRP78-targeted therapy as a novel strategy to overcome treatment resistance and improve clinical outcomes. GRP78-targeted therapy, either alone or in combination with conventional treatments, could be a novel and attractive strategy for future glioma treatment.
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