Targeting NF-kappaB in hematologic malignancies.
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.
Braun
T
T
Centre National de la Recherche Scientifique, UMR8125, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France.
Carvalho
G
G
Fabre
C
C
Grosjean
J
J
Fenaux
P
P
Kroemer
G
G
D019337:Hematologic Neoplasms / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000628:therapy; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000628:therapy; D008954:Models, Biological; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction
D016328:NF-kappa B