Advanced search
1 file | 385.95 KB

The kinase NIK as a therapeutic target in multiple myeloma

Sandra Gardam (UGent) and Rudi Beyaert (UGent)
Author
Organization
Project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
Introduction: Multiple myeloma (MM) is a neoplasm derived from B lymphocytes and often results in uncontrolled clonal expansion of antibody-secreting cells. While current treatments are able to prolong survival, MM remains incurable. Excessive NF-kappa B activity in MM contributes to tumor progression and survival. Areas covered: The contribution of NF-kappa B-inducing kinase (NIK) to alternative NF-kappa B signaling, where it is the key kinase, and classical NF-kappa B signaling. Modulation of NIK by natural and chemical factors and current and potential therapies for MM that target NIK. Expert opinion: Mutations affecting the activation of NIK have been identified in MM samples and cell lines, suggesting that NIK may be an important target for therapy of MM. NIK contributes to activation of both NF-kappa B pathways in MM, giving us the opportunity to limit two pathways contributing to oncogenic survival with a single therapeutic. Many of the mutations identified in MM cells result in the same outcome, hyperactive NIK, thus a single therapeutic may be effective in many patients even though they carry differing mutations. As NIK appears only to activate classical NF-kappa B when overexpressed, and in normal cells NIK levels are usually low, it is possible that therapeutics designed to limit the amount of NIK may not produce serious side effects in healthy cells.
Keywords
multiple myeloma, MAP3K14, NF-kappa B, NIK, therapy, NF-KAPPA-B, LYMPHOTOXIN-BETA-RECEPTOR, ALPHA-DEPENDENT APOPTOSIS, SECONDARY LYMPHOID ORGANS, IKK-ALPHA, NEGATIVE REGULATION, NF-KAPPA-B2 P100, TRANSACTIVATING ACTIVITY, TRANSCRIPTIONAL ACTIVITY, INDUCED ACTIVATION, inhibitor, cancer

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 385.95 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Gardam, Sandra, and Rudi Beyaert. 2011. “The Kinase NIK as a Therapeutic Target in Multiple Myeloma.” Expert Opinion on Therapeutic Targets 15 (2): 207–218.
APA
Gardam, S., & Beyaert, R. (2011). The kinase NIK as a therapeutic target in multiple myeloma. EXPERT OPINION ON THERAPEUTIC TARGETS, 15(2), 207–218.
Vancouver
1.
Gardam S, Beyaert R. The kinase NIK as a therapeutic target in multiple myeloma. EXPERT OPINION ON THERAPEUTIC TARGETS. 2011;15(2):207–18.
MLA
Gardam, Sandra, and Rudi Beyaert. “The Kinase NIK as a Therapeutic Target in Multiple Myeloma.” EXPERT OPINION ON THERAPEUTIC TARGETS 15.2 (2011): 207–218. Print.
@article{1187373,
  abstract     = {Introduction: Multiple myeloma (MM) is a neoplasm derived from B lymphocytes and often results in uncontrolled clonal expansion of antibody-secreting cells. While current treatments are able to prolong survival, MM remains incurable. Excessive NF-kappa B activity in MM contributes to tumor progression and survival.
Areas covered: The contribution of NF-kappa B-inducing kinase (NIK) to alternative NF-kappa B signaling, where it is the key kinase, and classical NF-kappa B signaling. Modulation of NIK by natural and chemical factors and current and potential therapies for MM that target NIK.
Expert opinion: Mutations affecting the activation of NIK have been identified in MM samples and cell lines, suggesting that NIK may be an important target for therapy of MM. NIK contributes to activation of both NF-kappa B pathways in MM, giving us the opportunity to limit two pathways contributing to oncogenic survival with a single therapeutic. Many of the mutations identified in MM cells result in the same outcome, hyperactive NIK, thus a single therapeutic may be effective in many patients even though they carry differing mutations. As NIK appears only to activate classical NF-kappa B when overexpressed, and in normal cells NIK levels are usually low, it is possible that therapeutics designed to limit the amount of NIK may not produce serious side effects in healthy cells.},
  author       = {Gardam, Sandra and Beyaert, Rudi},
  issn         = {1472-8222},
  journal      = {EXPERT OPINION ON THERAPEUTIC TARGETS},
  keywords     = {multiple myeloma,MAP3K14,NF-kappa B,NIK,therapy,NF-KAPPA-B,LYMPHOTOXIN-BETA-RECEPTOR,ALPHA-DEPENDENT APOPTOSIS,SECONDARY LYMPHOID ORGANS,IKK-ALPHA,NEGATIVE REGULATION,NF-KAPPA-B2 P100,TRANSACTIVATING ACTIVITY,TRANSCRIPTIONAL ACTIVITY,INDUCED ACTIVATION,inhibitor,cancer},
  language     = {eng},
  number       = {2},
  pages        = {207--218},
  title        = {The kinase NIK as a therapeutic target in multiple myeloma},
  url          = {http://dx.doi.org/10.1517/14728222.2011.548861},
  volume       = {15},
  year         = {2011},
}

Altmetric
View in Altmetric
Web of Science
Times cited: