Targeting NF-κB in hematologic malignancies

被引:144
作者
Braun, T
Carvalho, G
Fabre, C
Grosjean, J
Fenaux, P
Kroemer, G
机构
[1] Inst Gustave Roussy, UMR 8125, CNRS, F-94805 Villejuif, France
[2] Univ Paris 13, AP HP, Hop Avicenne, Hematol Unit, F-93000 Bobigny, France
关键词
lymphoid malignancies; myeloid malignancies; apoptosis; bortezomib; IKK antagonists;
D O I
10.1038/sj.cdd.4401874
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The transcription factor nuclear factor kappa B (NF-kappa B) 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-kappa B in lymphoid and myeloid malignancies, including preneoplastic conditions such as myelodysplastic syndromes, underscoring its implication in malignant transformation. Targeting intrinsic NF-kappa B 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-kappa B-activatory kinase I kappa B kinase, of the proteaseome, or of the DNA binding of NF-kappa B subunits are under intensive investigation. Currently used cytotoxic agents can induce NF-kappa B activation as an unwarranted side effect, which confers apoptosis suppression and hence resistance to these drugs. Thus, NF-kappa B inhibitory molecules may be clinically useful, either as single therapeutic agents or in combination with classical chemotherapeutic agents, for the treatment of hematological malignancies.
引用
收藏
页码:748 / 758
页数:11
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