Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 1,061

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Is NF-κB a good target for cancer therapy? Hopes and pitfalls

Open access
Baud, Véronique, Karin, Michael·2009·Nature Reviews Drug Discovery
DOI 10.1038/nrd2781
Open this paper in CoChat — free account

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nrd2781

Cites

10 of 10 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 10 references

Research works printed but not linked: 93

  1. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000). · DOI · Paper page
  2. Balkwill, F., Charles, K. A. & Mantovani, A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7, 211–217 (2005). · DOI · Paper page
  3. Karin, M. & Greten, F. R. NF-κB: linking inflammation and immunity to cancer development and progression. Nature Rev. Immunol. 5, 749–759 (2005). · DOI · Paper page
  4. Nicolau, M., Tibshirani, R., Borresen-Dale, A. L. & Jeffrey, S. S. Disease-specific genomic analysis: identifying the signature of pathologic biology. Bioinformatics 23, 957–965 (2007). · DOI
  5. Segal, E., Friedman, N., Kaminski, N., Regev, A. & Koller, D. From signatures to models: understanding cancer using microarrays. Nature Genet. 37 (Suppl.), S38–S45 (2005). · DOI · Paper page
  6. Lucito, R. et al. Representational oligonucleotide microarray analysis: a high-resolution method to detect genome copy number variation. Genome Res. 13, 2291–2305 (2003). · DOI · Paper page
  7. Wang, H., Han, H., Mousses, S. & Von Hoff, D. D. Targeting loss-of-function mutations in tumor-suppressor genes as a strategy for development of cancer therapeutic agents. Semin. Oncol. 33, 513–520 (2006). · DOI
  8. Wood, L. D. et al. The genomic landscapes of human breast and colorectal cancers. Science 318, 1108–1113 (2007). · DOI · Paper page
  9. Chanock, S. J. et al. Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas. Breast Cancer Res. 9, R5 (2007). · DOI
  10. Yosef, N. et al. A supervised approach for identifying discriminating genotype patterns and its application to breast cancer data. Bioinformatics 23, e91–e98 (2007). · DOI
  11. Druker, B. J. STI571 (Gleevec) as a paradigm for cancer therapy. Trends Mol. Med. 8, S14–S18 (2002). · DOI · Paper page
  12. Basseres, D. S. & Baldwin, A. S. Nuclear factor-κB and inhibitor of κB kinase pathways in oncogenic initiation and progression. Oncogene 25, 6817–6830 (2006). · DOI · Paper page
  13. Jost, P. J. & Ruland, J. Aberrant NF-κB signaling in lymphoma: mechanisms, consequences, and therapeutic implications. Blood 109, 2700–2707 (2007). · DOI · Paper page
  14. Cilloni, D., Martinelli, G., Messa, F., Baccarani, M. & Saglio, G. Nuclear factor κB as a target for new drug development in myeloid malignancies. Haematologica 92, 1224–1229 (2007). · DOI
  15. Dutta, J., Fan, Y., Gupta, N., Fan, G. & Gelinas, C. Current insights into the regulation of programmed cell death by NF-κB. Oncogene 25, 6800–6816 (2006). · DOI · Paper page
  16. Luo, J. L., Kamata, H. & Karin, M. The anti-death machinery in IKK/NF-κB signaling. J. Clin. Immunol. 25, 541–550 (2005). · DOI
  17. Burstein, E. & Duckett, C. S. Dying for NF-κB? Control of cell death by transcriptional regulation of the apoptotic machinery. Curr. Opin. Cell Biol. 15, 732–737 (2003). · DOI
  18. Lawrence, T., Bebien, M., Liu, G. Y., Nizet, V. & Karin, M. IKKα limits macrophage NF-κB activation and contributes to the resolution of inflammation. Nature 434, 1138–1143 (2005). · DOI · Paper page
  19. Pikarsky, E. et al. NF-κB functions as a tumour promoter in inflammation-associated cancer. Nature 431, 461–466 (2004). · DOI · Paper page
  20. Luo, J. L., Kamata, H. & Karin, M. IKK/NF-κB signaling: balancing life and death — a new approach to cancer therapy. J. Clin. Invest. 115, 2625–2632 (2005). · DOI · Paper page
  21. Nakanishi, C. & Toi, M. Nuclear factor-κB inhibitors as sensitizers to anticancer drugs. Nature Rev. Cancer 5, 297–309 (2005). · DOI · Paper page
  22. Ghosh, S., May, M. J. & Kopp, E. B. NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16, 225–260 (1998). · DOI · Paper page
  23. Baud, V. & Karin, M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol. 11, 372–377 (2001). · DOI · Paper page
  24. Bonizzi, G. & Karin, M. The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 25, 280–288 (2004). · DOI · Paper page
  25. Derudder, E. et al. RelB/p50 dimers are differentially regulated by tumor necrosis factor-α and lymphotoxin-β receptor activation. J. Biol. Chem. 278, 23278–23284 (2003). · DOI
  26. Dejardin, E. et al. The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways. Immunity 17, 525–535 (2002). · DOI · Paper page
  27. Xiao, G., Harhaj, E. W. & Sun, S. NF-κB-inducing kinase regulates the processing of NF-κB2 p100. Mol. Cell 7, 401–409 (2001). · DOI · Paper page
  28. Coope, H. J. et al. CD40 regulates the processing of NF-kappaB2 p100 to p52. EMBO J. 21, 5375–5385 (2002). · DOI · Paper page
  29. Claudio, E., Brown, K., Park, S., Wang, H. & Siebenlist, U. BAFF-induced NEMO-independent processing of NF-κB2 in maturing B cells. Nature Immunol. 3, 958–965 (2002). · DOI · Paper page
  30. Dejardin, E. The alternative NF-κB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochem. Pharmacol. 72, 1161–1179 (2006). · DOI · Paper page
  31. Pomerantz, J. L. & Baltimore, D. Two pathways to NF-κB. Mol. Cell 10, 693–695 (2002). · DOI · Paper page
  32. Kyle, R. A. & Rajkumar, S. V. Multiple myeloma. N. Engl. J. Med. 351, 1860–1873 (2004). · DOI · Paper page
  33. Engelhardt, M. & Mertelsmann, R. 160 years of multiple myeloma: progress and challenges. Eur. J. Cancer 42, 1507–1509 (2006). · doi:10.1016/j.ejca.2006.05.003
  34. Denz, U., Haas, P. S., Wasch, R., Einsele, H. & Engelhardt, M. State of the art therapy in multiple myeloma and future perspectives. Eur. J. Cancer 42, 1591–1600 (2006). · DOI
  35. Podar, K., Richardson, P. G., Hideshima, T., Chauhan, D. & Anderson, K. C. The malignant clone and the bone-marrow environment. Best Pract. Res. Clin. Haematol. 20, 597–612 (2007). · DOI
  36. Ni, H. et al. Analysis of expression of nuclear factor kappa B (NF-κB) in multiple myeloma: downregulation of NF-κB induces apoptosis. Br. J. Haematol. 115, 279–286 (2001). · DOI · Paper page
  37. Hideshima, T. et al. NF-κB as a therapeutic target in multiple myeloma. J. Biol. Chem. 277, 16639–16647 (2002). · DOI · Paper page
  38. Bharti, A. C., Donato, N., Singh, S. & Aggarwal, B. B. Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-κB and IκBα kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 101, 1053–1062 (2003). · DOI · Paper page
  39. Hideshima, T. et al. MLN120B, a novel IκB kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo. Clin. Cancer Res. 12, 5887–5894 (2006). · DOI
  40. Jourdan, M. et al. Targeting NF-κB pathway with an IKK2 inhibitor induces inhibition of multiple myeloma cell growth. Br. J. Haematol. 138, 160–168 (2007). · DOI
  41. Sanda, T. et al. Growth inhibition of multiple myeloma cells by a novel IκB kinase inhibitor. Clin. Cancer Res. 11, 1974–1982 (2005). · DOI
  42. Feng, R. et al. SDX-308, a nonsteroidal anti-inflammatory agent, inhibits NF-κB activity, resulting in strong inhibition of osteoclast formation/activity and multiple myeloma cell growth. Blood 109, 2130–2138 (2007). · DOI
  43. Dai, Y. et al. Interruption of the NF-κB pathway by Bay 11-7082 promotes UCN-01-mediated mitochondrial dysfunction and apoptosis in human multiple myeloma cells. Blood 103, 2761–2770 (2004). · DOI
  44. Mitsiades, N. et al. Biologic sequelae of nuclear factor-κB blockade in multiple myeloma: therapeutic applications. Blood 99, 4079–4086 (2002). · DOI · Paper page
  45. Chauhan, D. et al. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-κB. Blood 87, 1104–1112 (1996). · DOI · Paper page
  46. Landowski, T. H., Olashaw, N. E., Agrawal, D. & Dalton, W. S. Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-κB (RelB/p50) in myeloma cells. Oncogene 22, 2417–2421 (2003). · DOI · Paper page
  47. Vande Broek, I. et al. Bone marrow endothelial cells increase the invasiveness of human multiple myeloma cells through upregulation of MMP-9: evidence for a role of hepatocyte growth factor. Leukemia 18, 976–982 (2004). · DOI
  48. Hecht, M., von Metzler, I., Sack, K., Kaiser, M. & Sezer, O. Interactions of myeloma cells with osteoclasts promote tumour expansion and bone degradation through activation of a complex signalling network and upregulation of cathepsin K, matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA). Exp. Cell Res. 314, 1082–1093 (2008). · DOI
  49. Hideshima, T., Podar, K., Chauhan, D. & Anderson, K. C. Cytokines and signal transduction. Best Pract. Res. Clin. Haematol. 18, 509–524 (2005). · DOI
  50. Niesvizky, R. et al. The relationship between quality of response and clinical benefit for patients treated on the bortezomib arm of the international, randomized, phase 3 APEX trial in relapsed multiple myeloma. Br. J. Haematol. 143, 46–53 (2008). · DOI
  51. Richardson, P. G., Mitsiades, C., Schlossman, R., Munshi, N. & Anderson, K. New drugs for myeloma. Oncologist 12, 664–689 (2007). · DOI
  52. Hideshima, T., Chauhan, D., Schlossman, R., Richardson, P. & Anderson, K. C. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene 20, 4519–4527 (2001). · DOI · Paper page
  53. Hideshima, T. et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 61, 3071–3076 (2001).
  54. Mitsiades, N. et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood 101, 2377–2380 (2003). · DOI · Paper page
  55. Mulligan, G. et al. Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib. Blood 109, 3177–3188 (2007). · DOI · Paper page
  56. Hussein, M. A. et al. Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma. Br. J. Haematol. 125, 470–476 (2004). · DOI
  57. Keifer, J. A., Guttridge, D. C., Ashburner, B. P. & Baldwin, A. S. Jr. Inhibition of NF-κB activity by thalidomide through suppression of IκB kinase activity. J. Biol. Chem. 276, 22382–22387 (2001). · DOI · Paper page
  58. Annunziata, C. M. et al. Frequent engagement of the classical and alternative NF-κB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell 12, 115–130 (2007). · DOI · Paper page
  59. Liao, G., Zhang, M., Harhaj, E. W. & Sun, S. C. Regulation of the NF-κB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J. Biol. Chem. 279, 26243–26250 (2004). · DOI · Paper page
  60. He, J. Q. et al. Rescue of TRAF3-null mice by p100 NF-κB deficiency. J. Exp. Med. 203, 2413–2418 (2006). · DOI · Paper page
  61. He, J. Q., Saha, S. K., Kang, J. R., Zarnegar, B. & Cheng, G. Specificity of TRAF3 in its negative regulation of the noncanonical NF-κB pathway. J. Biol. Chem. 282, 3688–3694 (2007). · DOI
  62. Vallabhapurapu, S. et al. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling. Nature Immunol. 9, 1364–1370 (2008). · DOI · Paper page
  63. Vince, J. E. et al. IAP antagonists target cIAP1 to induce TNFα-dependent apoptosis. Cell 131, 682–693 (2007). · DOI · Paper page
  64. Shinkura, R. et al. Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-κB-inducing kinase. Nature Genet. 22, 74–77 (1999). · DOI · Paper page
  65. Karrer, U., Althage, A., Odermatt, B., Hengartner, H. & Zinkernagel, R. M. Immunodeficiency of alymphoplasia mice (aly/aly) in vivo: structural defect of secondary lymphoid organs and functional B cell defect. Eur. J. Immunol. 30, 2799–2807 (2000). · doi:10.1002/1521-4141(200010)30:10<2799::aid-immu2799>3.0.co;2-2
  66. Yamada, T. et al. Abnormal immune function of hemopoietic cells from alymphoplasia (aly) mice, a natural strain with mutant NF-κB-inducing kinase. J. Immunol. 165, 804–812 (2000). · DOI · Paper page
  67. Yin, L. et al. Defective lymphotoxin-β receptor-induced NF-κB transcriptional activity in NIK-deficient mice. Science 291, 2162–2165 (2001). · DOI · Paper page
  68. Sasaki, Y., Casola, S., Kutok, J. L., Rajewsky, K. & Schmidt-Supprian, M. TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology. J. Immunol. 173, 2245–2252 (2004). · DOI · Paper page
  69. Shulga-Morskaya, S. et al. B cell-activating factor belonging to the TNF family acts through separate receptors to support B cell survival and T cell-independent antibody formation. J. Immunol. 173, 2331–2341 (2004). · DOI · Paper page
  70. Gardam, S., Sierro, F., Basten, A., Mackay, F. & Brink, R. TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals delivered to B cells by the BAFF receptor. Immunity 28, 391–401 (2008). · DOI · Paper page
  71. Malinin, N. L., Boldin, M. P., Kovalenko, A. V. & Wallach, D. MAP3K-related kinase involved in NF-κB induction by TNF, CD95 and IL-1. Nature 385, 540–544 (1997). · DOI · Paper page
  72. Ramakrishnan, P., Wang, W. & Wallach, D. Receptor-specific signaling for both the alternative and the canonical NF-κB activation pathways by NF-κB-inducing kinase. Immunity 21, 477–489 (2004). · DOI · Paper page
  73. Wang, C. Y., Mayo, M. W., Korneluk, R. G., Goeddel, D. V. & Baldwin, A. S. Jr. NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281, 1680–1683 (1998). · DOI · Paper page
  74. Vaux, D. L. & Silke, J. IAPs, RINGs and ubiquitylation. Nature Rev. Mol. Cell Biol. 6, 287–297 (2005). · DOI · Paper page
  75. Shu, H. B., Takeuchi, M. & Goeddel, D. V. The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Proc. Natl Acad. Sci. USA 93, 13973–13978 (1996). · DOI · Paper page
  76. Rothe, M., Pan, M. G., Henzel, W. J., Ayres, T. M. & Goeddel, D. V. The TNFR2–TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 83, 1243–1252 (1995). · DOI · Paper page
  77. Rothe, M., Wong, S. C., Henzel, W. J. & Goeddel, D. V. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 78, 681–692 (1994). · DOI · Paper page
  78. Yang, Y., Fang, S., Jensen, J. P., Weissman, A. M. & Ashwell, J. D. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 288, 874–877 (2000). · DOI · Paper page
  79. Li, X., Yang, Y. & Ashwell, J. D. TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 416, 345–347 (2002). · DOI · Paper page
  80. Matsuzawa, A. et al. Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science 321, 663–668 (2008). · DOI · Paper page
  81. Conte, D. et al. Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival. Mol. Cell. Biol. 26, 699–708 (2006). · DOI · Paper page
  82. Conze, D. B. et al. Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo. Mol. Cell. Biol. 25, 3348–3356 (2005). · DOI · Paper page
  83. Zender, L. et al. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 125, 1253–1267 (2006). · DOI · Paper page
  84. Du, C., Fang, M., Li, Y., Li, L. & Wang, X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, 33–42 (2000). · DOI · Paper page
  85. Verhagen, A. M. et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102, 43–53 (2000). · DOI · Paper page
  86. Schimmer, A. D. et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 5, 25–35 (2004). · DOI · Paper page
  87. Chauhan, D. et al. Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM). Blood 109, 1220–1227 (2007). · DOI
  88. Li, L. et al. A small molecule Smac mimic potentiates TRAIL- and TNFα-mediated cell death. Science 305, 1471–1474 (2004). · DOI · Paper page
  89. Davis, R. E. & Staudt, L. M. Molecular diagnosis of lymphoid malignancies by gene expression profiling. Curr. Opin. Hematol. 9, 333–338 (2002). · DOI
  90. Keutgens, A., Robert, I., Viatour, P. & Chariot, A. Deregulated NF-κB activity in haematological malignancies. Biochem. Pharmacol. 72, 1069–1080 (2006). · DOI
  91. Karin, M., Yamamoto, Y. & Wang, Q. M. The IKK NF-κB system: a treasure trove for drug development. Nature Rev. Drug Discov. 3, 17–26 (2004). · DOI · Paper page
  92. Greten, F. R. et al. NF-κB is a negative regulator of IL-1β secretion as revealed by genetic and pharmacological inhibition of IKKβ. Cell 130, 918–931 (2007). · DOI · Paper page
  93. Sasaki, Y. et al. NIK overexpression amplifies, whereas ablation of its TRAF3-binding domain replaces BAFF:BAFF-R-mediated survival signals in B cells. Proc. Natl Acad. Sci. USA. 105, 10883–10888 (2008). · DOI

Cited by

See all 1,061

Metadata

Authors
Baud, V., & Karin, M.
Venue
Nature Reviews Drug Discovery
Publisher
Springer Science and Business Media LLC
Published
2009-01
Volume
8
Issue
1
Pages
33-40
ISSN
  • 1474-1776 (ISSN-L)
  • 1474-1784
DOI
10.1038/nrd2781
OpenAlex
W2074688366
Cited by
1,061
References
10
FWCI
3.46
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Is NF-κB a good target for cancer therapy? Hopes and pitfalls. https://app.cochat.ai/papers/10.1038/nrd2781
The paper
Baud, V., & Karin, M. (2009). Is NF-κB a good target for cancer therapy? Hopes and pitfalls. Nature Reviews Drug Discovery. https://doi.org/10.1038/nrd2781

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.