NF-kappaB and IKK as therapeutic targets in cancer.
The transcription factor NF-kappaB and associated regulatory factors (including IkappaB kinase subunits and the IkappaB family member Bcl-3) are strongly implicated in a variety of hematologic and solid tumor malignancies. A role for NF-kappaB in cancer cells appears to involve regulation of cell proliferation, control of apoptosis, promotion of angiogenesis, and stimulation of invasion/metastasis. Consistent with a role for NF-kappaB in oncogenesis are observations that inhibition of NF-kappaB alone or in combination with cancer therapies leads to tumor cell death or growth inhibition. However, other experimental data indicate that NF-kappaB can play a tumor suppressor role in certain settings and that it can be important in promoting an apoptotic signal downstream of certain cancer therapy regimens. In order to appropriately move NF-kappaB inhibitors in the clinic, thorough approaches must be initiated to determine the molecular mechanisms that dictate the complexity of oncologic and therapeutic outcomes that are controlled by NF-kappaB.
Kim
H J
HJ
Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Hawke
N
N
Baldwin
A S
AS
D017209:Apoptosis; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D012680:Sensitivity and Specificity; D015398:Signal Transduction
D016328:NF-kappa B; D051550:I-kappa B Kinase