Abstract
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.
© 2012 John Wiley & Sons A/S.
Publication types
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Research Support, N.I.H., Intramural
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Review
MeSH terms
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Animals
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Antineoplastic Agents / therapeutic use
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CARD Signaling Adaptor Proteins / genetics
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Caspases / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism
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Leukemia, Lymphoid / drug therapy
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Leukemia, Lymphoid / genetics
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Leukemia, Lymphoid / metabolism*
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Lymphoma / drug therapy
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Lymphoma / genetics
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Lymphoma / metabolism*
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Lymphoma, Large B-Cell, Diffuse / metabolism
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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Mutation
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Myeloid Differentiation Factor 88 / genetics
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Neoplasm Proteins / metabolism
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Protein Kinase Inhibitors / therapeutic use
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Receptors, Antigen, B-Cell / metabolism
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Signal Transduction
Substances
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Antineoplastic Agents
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CARD Signaling Adaptor Proteins
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Intracellular Signaling Peptides and Proteins
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Myeloid Differentiation Factor 88
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NF-kappa B
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Neoplasm Proteins
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Protein Kinase Inhibitors
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Receptors, Antigen, B-Cell
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Caspases
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MALT1 protein, human
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein