Suppr超能文献

分子通路:在慢性淋巴细胞白血病中靶向磷酸肌醇 3-激酶 p110-delta。

Molecular pathways: targeting phosphoinositide 3-kinase p110-delta in chronic lymphocytic leukemia.

机构信息

Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA.

出版信息

Clin Cancer Res. 2012 Aug 1;18(15):4013-8. doi: 10.1158/1078-0432.CCR-11-1402. Epub 2012 Jun 18.

Abstract

The advent of targeted therapy, specifically to the B-cell receptor (BCR), has changed the convention for the treatment of chronic lymphocytic leukemia (CLL). The phosphoinositide 3-kinase (PI3K) pathway, activated upstream by the BCR, receptor tyrosine kinases, and cytokine receptors, has been a potential target for a multitude of cancers, but until the recent introduction of isoform-specific inhibitors has not been widely used. In this review, we focus on describing the intricate upstream and downstream signaling, leading to cell survival mediated by PI3K in B cells with a specific focus on the impact and importance of the p110δ isoform (which is localized to hematopoietic cells and regulates distinct cellular functions in B cells). In addition, the clinical advances from targeting p110δ are described, with a focus on clinical outcome, toxicities, and rational combination therapies. The experiences with p110δ in CLL have led to a more fundamental understanding of CLL signaling defects and may be predictive of other BCR-directed therapeutics.

摘要

靶向治疗的出现,特别是针对 B 细胞受体(BCR)的靶向治疗,改变了慢性淋巴细胞白血病(CLL)的治疗常规。磷酸肌醇 3-激酶(PI3K)途径在上游被 BCR、受体酪氨酸激酶和细胞因子受体激活,已成为多种癌症的潜在靶点,但直到最近才引入了同工型特异性抑制剂,尚未得到广泛应用。在这篇综述中,我们专注于描述导致 B 细胞中 PI3K 介导的细胞存活的复杂上游和下游信号传导,特别关注 p110δ 同工型(定位于造血细胞并调节 B 细胞中的独特细胞功能)的影响和重要性。此外,还描述了针对 p110δ 的临床进展,重点是临床结果、毒性和合理的联合治疗。在 CLL 中针对 p110δ 的经验使我们对 CLL 信号传导缺陷有了更深入的了解,并且可能对其他 BCR 靶向治疗具有预测性。

相似文献

4
The PI3K pathway: clinical inhibition in chronic lymphocytic leukemia.PI3K通路:慢性淋巴细胞白血病中的临床抑制作用
Semin Oncol. 2016 Apr;43(2):260-4. doi: 10.1053/j.seminoncol.2016.02.004. Epub 2016 Feb 8.

引用本文的文献

本文引用的文献

7
AKT/PKB signaling: navigating downstream.AKT/蛋白激酶B信号传导:下游通路解析
Cell. 2007 Jun 29;129(7):1261-74. doi: 10.1016/j.cell.2007.06.009.

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验