title: Pathogenetic importance and therapeutic implications of NF-κB in lymphoid malignancies.
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.
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kian-Huat
authors.initials: KH
authors.lastname: Lim
authors.forename: Yibin
authors.initials: Y
authors.lastname: Yang
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D053468:CARD Signaling Adaptor Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein