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:AXL: A novel therapeutic target in IBD.
AXL: A novel therapeutic target in IBD.
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炎症性肠病(IBD)及其后遗症(结肠炎相关癌和纤维狭窄性并发症)仍然是重大的临床挑战,迫切需要新的治疗靶点。AXL是一种受体酪氨酸激酶,已被认为参与IBD发病机制中众多核心细胞功能。这些功能包括促进上皮-间质转化、抑制Toll样受体和NK 细胞介导的免疫反应、驱动增殖以及传播纤维化信号。绝大多数关于AXL的临床前研究都集中在其在癌症中的作用。因此,药理学AXL抑制剂目前正处于临床试验阶段,但适应症仍局限于恶性肿瘤。在本章中,我们总结了AXL在IBD、结肠炎相关癌和纤维狭窄性疾病中的当前临床前数据,并强调其作为新型治疗靶点的潜力。
Inflammatory bowel diseases (IBD) and their sequela (colitis-associate carcinoma and fibrostenotic complications) remain a significant clinical challenge and novel therapeutic targets are desperately needed. AXL, a receptor tyrosine kinase, has been implicated in myriad cellular functions central to the pathogenesis of IBD. These include facilitating epithelial-to-mesenchymal transition, dampening of Toll-like receptor and natural killer cell mediated immune responses, driving proliferation, and propagating fibrogenic signaling.
The vast majority of preclinical research on AXL has focused on its role in cancer. As such, pharmacologic AXL inhibitors are currently in clinical trials, but the indications remain limited to malignancy. In this chapter, we summarize the current preclinical data of AXL in IBD, colitis associated carcinoma, and fibrostenotic disease, and highlight its potential as a novel therapeutic target.
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