title: NF-κB dysregulation in multiple myeloma.
abstract: The nuclear factor-κB (NF-κB) transcription factor family plays critical roles in the pathophysiology of hematologic neoplasias, including multiple myeloma. The current review examines the roles that this transcription factor system plays in multiple myeloma cells and the nonmalignant accessory cells of the local microenvironment; as well as the evidence indicating that a large proportion of myeloma patients harbor genomic lesions which perturb diverse genes regulating the activity of NF-κB. This article also discusses the therapeutic targeting of the NF-κB pathway using proteasome inhibitors, a pharmacological class that has become a cornerstone in the therapeutic management of myeloma; and reviews some of the future challenges and opportunities for NF-κB-related research in myeloma.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, United States.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Matthews
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, United States.
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Matos Simoes
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, United States.
authors.forename: Eugen
authors.initials: E
authors.lastname: Dhimolea
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, United States.
authors.forename: Michal
authors.initials: M
authors.lastname: Sheffer
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, United States.
authors.forename: Sara
authors.initials: S
authors.lastname: Gandolfi
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, United States.
authors.forename: Olga
authors.initials: O
authors.lastname: Dashevsky
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Sorrell
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, United States. Electronic address: Constantine_Mitsiades@dfci.harvard.edu.
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Mitsiades
mesh_terms: D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D016328:NF-kappa B
keywords: Microenvironment; Myeloma; NF-kappaB; Proteasome inhibitors; Stromal cells