Bejan J Saeedi, Hannah E Carr, Peter D R Higgins, Calen A Steiner
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引用次数: 0
摘要
炎症性肠病(IBD)及其后遗症(结肠炎相关癌变和纤维化并发症)仍然是一项重大的临床挑战,迫切需要新的治疗靶点。AXL是一种受体酪氨酸激酶,与IBD发病机制中的多种细胞功能有关。这些功能包括促进上皮细胞向间质转化、抑制 Toll 样受体和自然杀伤细胞介导的免疫反应、驱动增殖以及传播纤维化信号。有关 AXL 的绝大多数临床前研究都集中于其在癌症中的作用。因此,药理 AXL 抑制剂目前正处于临床试验阶段,但其适应症仍仅限于恶性肿瘤。在本章中,我们将总结 AXL 目前在肠道疾病、结肠炎相关癌和纤维化疾病中的临床前数据,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.