Braun T, Carvalho G, Fabre C, Grosjean J, Fenaux P, Kroemer G
Centre National de la Recherche Scientifique, UMR8125, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France.
Cell Death Differ. 2006 May;13(5):748-58. doi: 10.1038/sj.cdd.4401874.
The transcription factor nuclear factor kappa B (NF-kappaB) can intervene in oncogenesis by virtue of its capacity to regulate the expression of a plethora of genes that modulate apoptosis, and cell survival as well as proliferation, inflammation, tumor metastasis and angiogenesis. Different reports demonstrate the intrinsic activation of NF-kappaB in lymphoid and myeloid malignancies, including preneoplastic conditions such as myelodysplastic syndromes, underscoring its implication in malignant transformation. Targeting intrinsic NF-kappaB activation, as well as its upstream and downstream regulators, may hence constitute an additional approach to the oncologist's armamentarium. Several small inhibitors of the NF-kappaB-activatory kinase IkappaB kinase, of the proteasome, or of the DNA binding of NF-kappaB subunits are under intensive investigation. Currently used cytotoxic agents can induce NF-kappaB activation as an unwarranted side effect, which confers apoptosis suppression and hence resistance to these drugs. Thus, NF-kappaB inhibitory molecules may be clinically useful, either as single therapeutic agents or in combination with classical chemotherapeutic agents, for the treatment of hematological malignancies.
转录因子核因子κB（NF-κB）可通过调节众多基因的表达来干预肿瘤发生，这些基因可调节细胞凋亡、细胞存活以及增殖、炎症、肿瘤转移和血管生成。不同的报告表明，NF-κB在淋巴和髓系恶性肿瘤中存在内在激活，包括如骨髓增生异常综合征等肿瘤前期病症，这突出了其在恶性转化中的作用。因此，靶向NF-κB的内在激活及其上游和下游调节因子，可能成为肿瘤学家治疗手段中的一种额外方法。几种针对NF-κB激活激酶IκB激酶、蛋白酶体或NF-κB亚基DNA结合的小分子抑制剂正在深入研究中。目前使用的细胞毒性药物可诱导NF-κB激活，这是一种不必要的副作用，它会抑制细胞凋亡，从而导致对这些药物产生耐药性。因此，NF-κB抑制分子可能在临床上有用，无论是作为单一治疗药物还是与经典化疗药物联合使用，用于治疗血液系统恶性肿瘤。
