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

Abstract

Nuclear factor κB (NF-κB) transcription factors have a key role in many physiological processes such as innate and adaptive immune responses, cell proliferation, cell death, and inflammation. It has become clear that aberrant regulation of NF-κB and the signalling pathways that control its activity are involved in cancer development and progression, as well as in resistance to chemotherapy and radiotherapy. This article discusses recent evidence from cancer genetics and cancer genome studies that support the involvement of NF-κB in human cancer, particularly in multiple myeloma. The therapeutic potential and benefit of targeting NF-κB in cancer, and the possible complications and pitfalls of such an approach, are explored.

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Figure 1: NF-κB target genes involved in cancer development and progression.
Figure 2: NF-κB gain- and loss-of-function mutations in multiple myeloma.
Figure 3: IAPs and IAP antagonists in the regulation of NF-κB and cell death pathways.

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References

  1. World Health Organization (WHO) and International Union Against Cancer (UICC). Global Action Against Cancer. (WHO/UICC, Geneva, Switzerland, 2005).

  2. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).

    CAS  PubMed  Google Scholar 

  3. 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).

    Article  CAS  PubMed  Google Scholar 

  4. Lin, W. W. & Karin, M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J. Clin. Invest. 117, 1175–1183 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Karin, M. & Greten, F. R. NF-κB: linking inflammation and immunity to cancer development and progression. Nature Rev. Immunol. 5, 749–759 (2005).

    CAS  Google Scholar 

  6. 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).

    CAS  PubMed  Google Scholar 

  7. 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).

    CAS  PubMed  Google Scholar 

  8. Lucito, R. et al. Representational oligonucleotide microarray analysis: a high-resolution method to detect genome copy number variation. Genome Res. 13, 2291–2305 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Weir, B. A. et al. Characterizing the cancer genome in lung adenocarcinoma. Nature 450, 893–898 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 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).

    CAS  PubMed  Google Scholar 

  11. Wood, L. D. et al. The genomic landscapes of human breast and colorectal cancers. Science 318, 1108–1113 (2007).

    CAS  PubMed  Google Scholar 

  12. 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).

    PubMed  PubMed Central  Google Scholar 

  13. Yosef, N. et al. A supervised approach for identifying discriminating genotype patterns and its application to breast cancer data. Bioinformatics 23, e91–e98 (2007).

    CAS  PubMed  Google Scholar 

  14. Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783–792 (2001).

    CAS  PubMed  Google Scholar 

  15. Izumi, Y., Xu, L., di Tomaso, E., Fukumura, D. & Jain, R. K. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 416, 279–280 (2002).

    CAS  PubMed  Google Scholar 

  16. Druker, B. J. STI571 (Gleevec) as a paradigm for cancer therapy. Trends Mol. Med. 8, S14–S18 (2002).

    CAS  PubMed  Google Scholar 

  17. 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).

    CAS  PubMed  Google Scholar 

  18. Jost, P. J. & Ruland, J. Aberrant NF-κB signaling in lymphoma: mechanisms, consequences, and therapeutic implications. Blood 109, 2700–2707 (2007).

    CAS  PubMed  Google Scholar 

  19. 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).

    CAS  PubMed  Google Scholar 

  20. 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).

    CAS  PubMed  Google Scholar 

  21. Luo, J. L., Kamata, H. & Karin, M. The anti-death machinery in IKK/NF-κB signaling. J. Clin. Immunol. 25, 541–550 (2005).

    CAS  PubMed  Google Scholar 

  22. 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).

    CAS  PubMed  Google Scholar 

  23. Greten, F. R. et al. IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118, 285–296 (2004).

    CAS  PubMed  Google Scholar 

  24. Karin, M. Nuclear factor-κB in cancer development and progression. Nature 441, 431–436 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. 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).

    CAS  PubMed  Google Scholar 

  26. Pikarsky, E. et al. NF-κB functions as a tumour promoter in inflammation-associated cancer. Nature 431, 461–466 (2004).

    CAS  PubMed  Google Scholar 

  27. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Nakanishi, C. & Toi, M. Nuclear factor-κB inhibitors as sensitizers to anticancer drugs. Nature Rev. Cancer 5, 297–309 (2005).

    CAS  Google Scholar 

  29. 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).

    CAS  PubMed  Google Scholar 

  30. Ghosh, S. & Karin, M. Missing pieces in the NF-κB puzzle. Cell 109 (Suppl.), S81–S96 (2002).

    CAS  PubMed  Google Scholar 

  31. Baud, V. & Karin, M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol. 11, 372–377 (2001).

    CAS  PubMed  Google Scholar 

  32. Bonizzi, G. & Karin, M. The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 25, 280–288 (2004).

    CAS  PubMed  Google Scholar 

  33. 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).

    CAS  PubMed  Google Scholar 

  34. Dejardin, E. et al. The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways. Immunity 17, 525–535 (2002).

    CAS  PubMed  Google Scholar 

  35. Xiao, G., Harhaj, E. W. & Sun, S. NF-κB-inducing kinase regulates the processing of NF-κB2 p100. Mol. Cell 7, 401–409 (2001).

    CAS  PubMed  Google Scholar 

  36. Coope, H. J. et al. CD40 regulates the processing of NF-kappaB2 p100 to p52. EMBO J. 21, 5375–5385 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 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).

    CAS  Google Scholar 

  38. Dejardin, E. The alternative NF-κB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochem. Pharmacol. 72, 1161–1179 (2006).

    CAS  PubMed  Google Scholar 

  39. Pomerantz, J. L. & Baltimore, D. Two pathways to NF-κB. Mol. Cell 10, 693–695 (2002).

    CAS  PubMed  Google Scholar 

  40. Kyle, R. A. & Rajkumar, S. V. Multiple myeloma. N. Engl. J. Med. 351, 1860–1873 (2004).

    CAS  PubMed  Google Scholar 

  41. Engelhardt, M. & Mertelsmann, R. 160 years of multiple myeloma: progress and challenges. Eur. J. Cancer 42, 1507–1509 (2006).

    PubMed  Google Scholar 

  42. 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).

    PubMed  Google Scholar 

  43. 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).

    CAS  PubMed  Google Scholar 

  44. 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).

    CAS  PubMed  Google Scholar 

  45. Hideshima, T. et al. NF-κB as a therapeutic target in multiple myeloma. J. Biol. Chem. 277, 16639–16647 (2002).

    CAS  PubMed  Google Scholar 

  46. 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).

    CAS  PubMed  Google Scholar 

  47. 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).

    CAS  PubMed  Google Scholar 

  48. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Sanda, T. et al. Growth inhibition of multiple myeloma cells by a novel IκB kinase inhibitor. Clin. Cancer Res. 11, 1974–1982 (2005).

    CAS  PubMed  Google Scholar 

  50. 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).

    CAS  PubMed  Google Scholar 

  51. 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).

    CAS  PubMed  Google Scholar 

  52. Mitsiades, N. et al. Biologic sequelae of nuclear factor-κB blockade in multiple myeloma: therapeutic applications. Blood 99, 4079–4086 (2002).

    CAS  PubMed  Google Scholar 

  53. 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).

    CAS  PubMed  Google Scholar 

  54. 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).

    CAS  PubMed  Google Scholar 

  55. 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).

    CAS  PubMed  Google Scholar 

  56. 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).

    CAS  PubMed  Google Scholar 

  57. Hideshima, T., Podar, K., Chauhan, D. & Anderson, K. C. Cytokines and signal transduction. Best Pract. Res. Clin. Haematol. 18, 509–524 (2005).

    CAS  PubMed  Google Scholar 

  58. 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).

    CAS  PubMed  Google Scholar 

  59. Richardson, P. G., Mitsiades, C., Schlossman, R., Munshi, N. & Anderson, K. New drugs for myeloma. Oncologist 12, 664–689 (2007).

    CAS  PubMed  Google Scholar 

  60. 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).

    CAS  PubMed  Google Scholar 

  61. 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).

    CAS  PubMed  Google Scholar 

  62. 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).

    CAS  PubMed  Google Scholar 

  63. Mulligan, G. et al. Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib. Blood 109, 3177–3188 (2007).

    CAS  PubMed  Google Scholar 

  64. 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).

    CAS  PubMed  Google Scholar 

  65. 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).

    CAS  PubMed  Google Scholar 

  66. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Keats, J. J. et al. Promiscuous mutations activate the noncanonical NF-κB pathway in multiple myeloma. Cancer Cell 12, 131–144 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 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).

    CAS  PubMed  Google Scholar 

  69. He, J. Q. et al. Rescue of TRAF3-null mice by p100 NF-κB deficiency. J. Exp. Med. 203, 2413–2418 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 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).

    CAS  PubMed  Google Scholar 

  71. 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).

    CAS  Google Scholar 

  72. Varfolomeev, E. et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-κB activation, and TNFα-dependent apoptosis. Cell 131, 669–681 (2007).

    CAS  PubMed  Google Scholar 

  73. Vince, J. E. et al. IAP antagonists target cIAP1 to induce TNFα-dependent apoptosis. Cell 131, 682–693 (2007).

    CAS  PubMed  Google Scholar 

  74. 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).

    CAS  PubMed  Google Scholar 

  75. 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).

    CAS  PubMed  Google Scholar 

  76. 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).

    CAS  PubMed  Google Scholar 

  77. Yin, L. et al. Defective lymphotoxin-β receptor-induced NF-κB transcriptional activity in NIK-deficient mice. Science 291, 2162–2165 (2001).

    CAS  PubMed  Google Scholar 

  78. 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).

    CAS  PubMed  Google Scholar 

  79. 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).

    CAS  PubMed  Google Scholar 

  80. 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).

    CAS  PubMed  Google Scholar 

  81. 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).

    CAS  PubMed  Google Scholar 

  82. 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).

    CAS  PubMed  Google Scholar 

  83. 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).

    CAS  PubMed  Google Scholar 

  84. Vaux, D. L. & Silke, J. IAPs, RINGs and ubiquitylation. Nature Rev. Mol. Cell Biol. 6, 287–297 (2005).

    CAS  Google Scholar 

  85. Hunter, A. M., LaCasse, E. C. & Korneluk, R. G. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis 12, 1543–1568 (2007).

    CAS  PubMed  Google Scholar 

  86. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 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).

    CAS  PubMed  Google Scholar 

  88. 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).

    CAS  PubMed  Google Scholar 

  89. 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).

    CAS  PubMed  Google Scholar 

  90. Li, X., Yang, Y. & Ashwell, J. D. TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 416, 345–347 (2002).

    PubMed  Google Scholar 

  91. Matsuzawa, A. et al. Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science 321, 663–668 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Conte, D. et al. Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival. Mol. Cell. Biol. 26, 699–708 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Zender, L. et al. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 125, 1253–1267 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 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).

    CAS  PubMed  Google Scholar 

  96. 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).

    CAS  PubMed  Google Scholar 

  97. Schimmer, A. D. et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 5, 25–35 (2004).

    CAS  PubMed  Google Scholar 

  98. Chauhan, D. et al. Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM). Blood 109, 1220–1227 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Li, L. et al. A small molecule Smac mimic potentiates TRAIL- and TNFα-mediated cell death. Science 305, 1471–1474 (2004).

    CAS  PubMed  Google Scholar 

  100. Davis, R. E. & Staudt, L. M. Molecular diagnosis of lymphoid malignancies by gene expression profiling. Curr. Opin. Hematol. 9, 333–338 (2002).

    PubMed  Google Scholar 

  101. Keutgens, A., Robert, I., Viatour, P. & Chariot, A. Deregulated NF-κB activity in haematological malignancies. Biochem. Pharmacol. 72, 1069–1080 (2006).

    CAS  PubMed  Google Scholar 

  102. 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).

    CAS  Google Scholar 

  103. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Our apologies to colleagues whose important contributions are not cited owing to space constraints. Many thanks to H. Authier and A. Moore for invaluable technical assistance. This work was supported by grants from the National Institutes of Health and the American Association for Cancer Research (to M.K.), and L'Agence Nationale pour la Recherche, Association pour la Recherche sur le Cancer, Belgian InterUniversity Attraction Pole, Ministère de la Recherche/Cancéropole IdF, and Université Paris Descartes (to V.B.).

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Baud, V., Karin, M. Is NF-κB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 8, 33–40 (2009). https://doi.org/10.1038/nrd2781

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