NF-κB 作为慢性淋巴细胞白血病的治疗靶点。
NF-kappaB as a therapeutic target in chronic lymphocytic leukemia.
机构信息
Hematopathology Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Spain.
出版信息
Expert Opin Ther Targets. 2010 Mar;14(3):275-88. doi: 10.1517/14728221003598930.
IMPORTANCE OF THE FIELD
NF-kappaB includes a family of transcription factors that play a critical role in the biology of normal lymphocytes and it is aberrantly activated in chronic lymphocytic leukemia (CLL) cells. Here, we review the role of constitutive NF-kappaB activation in CLL pathogenesis and its potential as a therapeutic target for CLL treatment.
AREAS COVERED IN THIS REVIEW
This review highlights the different strategies reported to inhibit NF-kappaB signaling in CLL cells. They include both IkappaB kinase inhibitors and several natural compounds that act at different steps of the pathway.
WHAT THE READER WILL GAIN
Targeting NF-kappaB leads to apoptosis of CLL cells, corroborating the role of NF-kappaB in the survival and clonal expansion of these tumoral cells. Moreover, several studies confirmed a synergistic effect between NF-kappaB inhibitors and other antitumoral agents and that inhibition of NF-kappaB could overcome the microenvironmental protection of CLL cells.
TAKE HOME MESSAGE
NF-kappaB is a relevant target in CLL and inhibitors of this prosurvival pathway, alone or in combination, represent a novel therapeutic strategy for the treatment of CLL patients.
重要性领域
NF-κB 包括转录因子家族，在正常淋巴细胞的生物学中起着关键作用，并且在慢性淋巴细胞白血病 (CLL) 细胞中异常激活。在这里，我们回顾了组成性 NF-κB 激活在 CLL 发病机制中的作用及其作为 CLL 治疗的治疗靶点的潜力。
本篇综述涵盖的领域
本篇综述强调了报道的抑制 CLL 细胞中 NF-κB 信号的不同策略。它们包括 IκB 激酶抑制剂和几种在该途径的不同步骤起作用的天然化合物。
读者将获得的收益
靶向 NF-κB 导致 CLL 细胞凋亡，这证实了 NF-κB 在这些肿瘤细胞的存活和克隆扩增中的作用。此外，几项研究证实了 NF-κB 抑制剂与其他抗肿瘤药物之间的协同作用，并且抑制 NF-κB 可以克服 CLL 细胞的微环境保护。
结论
NF-κB 是 CLL 的一个相关靶点，该生存途径的抑制剂单独或联合使用，代表了治疗 CLL 患者的一种新的治疗策略。
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