Pathogenetic importance and therapeutic implications of NF-κB in lymphoid malignancies.
Pathogenetic importance and therapeutic implications of NF-κB in lymphoid malignancies.
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DOI：
10.1111/j.1600-065x.2012.01105.x
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发表时间：
2012-03
影响因子：
8.7
通讯作者：
Staudt LM
中科院分区：
文献类型：
--
作者：
Lim KH;Yang Y;Staudt LM
核因子κB(NF-κB)途径的错位启动和/或维持了多种类型的人类癌症。B细胞恶性肿瘤尤其受到致癌基因突变、易位和拷贝数改变的影响，这些因素影响了关键成分--NF-κB途径，这很可能是由于该途径在正常B细胞中的普遍作用。这些基因异常导致肿瘤对核因子-κB上瘾，这可以用于治疗。由于每种类型的淋巴癌使用不同的机制来激活NF-κB，因此需要几种不同的治疗策略来解决这种发病机制的异质性。幸运的是，一些阻断导致核因子-κB的信号级联反应的药物正处于早期临床试验阶段，其中几种药物已经在淋巴系统恶性肿瘤中显示出活性。
Derangement of the nuclear factor κB (NF-κB) pathway initiates and/or sustains many types of human cancer. B-cell malignancies are particularly affected by oncogenic mutations, translocations, and copy number alterations affecting key components the NF-κB pathway, most likely owing to the pervasive role of this pathway in normal B cells. These genetic aberrations cause tumors to be ‘addicted’ to NF-κB, which can be exploited therapeutically. Since each subtype of lymphoid cancer utilizes different mechanisms to activate NF-κB, several different therapeutic strategies are needed to address this pathogenetic heterogeneity. Fortunately, a number of drugs that block signaling cascades leading to NF-κB are in early phase clinical trials, several of which are already showing activity in lymphoid malignancies.