Clinical and Translational Oncology

, Volume 10, Issue 3, pp 143–147 | Cite as

The role of the NFκB signalling pathway in cancer

  • María Cortés Sempere
  • Vanesa Rodríguez Fanjul
  • Isabel Sánchez Pérez
  • Rosario Perona
Educational Series


The nuclear factor kappa B (NFκB) signalling pathway regulates the expression of hundreds of genes that are involved in different cellular processes such as cell proliferation, survival, stress responses, cellular immunity and inflammation. Its aberrant regulation is involved in several pathologies, but its relevance in cellular transformation and cancer development has been extensively studied. Mutations in the core components of NFκB as well as in the cellular machinery that regulates its activation have been found in many types of tumours. On the other hand, its role in promoting cell survival is an important obstacle in many cancer therapies. The development of chemical inhibitors that block NFκB activation acting either directly on IKKs or on the proteosome machinery has shown antitumour and proapoptotic activity both in preclinical and clinical studies.


rel NFκB IκB Bortezomib IKK 


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  1. 1.
    Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8:49–62PubMedCrossRefGoogle Scholar
  2. 2.
    Bonizzi G, Karin M (2004) The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25:280–288PubMedCrossRefGoogle Scholar
  3. 3.
    Hayden MS, Ghosh S (2004) Signaling to NF-kappaB. Genes Dev 18:2195–2224PubMedCrossRefGoogle Scholar
  4. 4.
    Perkins ND (2003) Oncogenes, tumor suppressors and p52 NF-kappaB. Oncogene 22:7553–7556PubMedCrossRefGoogle Scholar
  5. 5.
    Kalaitzidis D, Ok J, Sulak L 2nd et al (2004) Characterization of a human REL-estrogen receptor fusion protein with a reverse conditional transforming activity in chicken spleen cells. Oncogene 23:7580–7587PubMedCrossRefGoogle Scholar
  6. 6.
    Fukuhara N, Tagawa H, Kameoka Y et al (2006) Characterization of target genes at the 2p15-16 amplicon in diffuse large B-cell lymphoma. Cancer Sci 97:499–504PubMedCrossRefGoogle Scholar
  7. 7.
    Barth TF, Bentz M, Leithäuser F et al (2001) Molecular-cytogenetic comparison of mucosa-associated marginal zone B-cell lymphoma and large B-cell lymphoma arising in the gastro-intestinal tract. Genes Chromosomes Cancer 31:316–325PubMedCrossRefGoogle Scholar
  8. 8.
    Neri A, Fracchiolla NS, Migliazza A et al (1996) The involvement of the candidate proto-oncogene NFKB2/lyt-10 in lymphoid malignancies. Leuk Lymphoma 23:43–48PubMedCrossRefGoogle Scholar
  9. 9.
    Hinz M, Löser P, Mathas S et al (2001) Constitutive NF-kappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells. Blood 97:2798–2807PubMedCrossRefGoogle Scholar
  10. 10.
    Bours V, Franzoso G, Azarenko V et al (1993). The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers. Cell 72: 729–739PubMedCrossRefGoogle Scholar
  11. 11.
    Van Waes C (2007). Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res 13:1076–1082PubMedCrossRefGoogle Scholar
  12. 12.
    Wang CY, Mayo MW, Korneluk RG et al (1998). NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281:1680–1683PubMedCrossRefGoogle Scholar
  13. 13.
    Guttridge DC, Albanese C, Reuther JY et al (1999) NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol 19:5785–5799PubMedGoogle Scholar
  14. 14.
    Chen C, Edelstein LC, Gélinas C (2000) The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x(L). Mol Cell Biol 20:2687–2695PubMedCrossRefGoogle Scholar
  15. 15.
    Richardson PG, Mitsiades C, Hideshima T, Anderson KC (2006) Bortezomib: proteasome inhibition as an effective anticancer therapy. Annu Rev Med 57:33–47PubMedCrossRefGoogle Scholar
  16. 16.
    Papandreou CN, Daliani DD, Nix D et al (2004) Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J Clin Oncol 22:2108–2121PubMedCrossRefGoogle Scholar
  17. 17.
    Davis NB, Taber DA, Ansari RH et al (2004). Phase II trial of PS-341 in patients with renal cell cancer: a University of Chicago phase II consortium study. J Clin Oncol 22:115–119PubMedCrossRefGoogle Scholar
  18. 18.
    Kondagunta GV, Drucker B, Schwartz L et al (2004) Phase II trial of bortezomib for patients with advanced renal cell carcinoma. J Clin Oncol 22:3720–3725PubMedCrossRefGoogle Scholar
  19. 19.
    Markovic SN, Geyer SM, Dawkins F et al (2005) A phase II study of bortezomib in the treatment of metastatic malignant melanoma. Cancer 103:2584–2589PubMedCrossRefGoogle Scholar
  20. 20.
    Mackay H, Hedley D, Major P et al (2005) A phase II trial with pharmacodynamic endpoints of the proteasome inhibitor bortezomib in patients with metastatic colorectal cancer. Clin Cancer Res 11:5526–5533PubMedCrossRefGoogle Scholar
  21. 21.
    Yang CH, Gonzalez-Angulo AM, Reuben JM et al (2006) Bortezomib (VELCADE) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. Ann Oncol 17:813–817PubMedCrossRefGoogle Scholar
  22. 22.
    Ramirez PT, Landen CN Jr, Coleman RL et al (2008). Phase I trial of the proteasome inhibitor bortezomib in combination with carboplatin in patients with platinum-and taxane-resistant ovarian cancer. Gynecol Oncol 108:68–71PubMedCrossRefGoogle Scholar
  23. 23.
    Davies AM, Ho C, Metzger AS et al (2007) Phase I study of two different schedules of bortezomib and pemetrexed in advanced solid tumors with emphasis on non-small cell lung cancer. J Thorac Oncol 2:1112–1116PubMedGoogle Scholar
  24. 24.
    Davies AM, Ruel C, Lara PN et al (2008) The proteasome inhibitor bortezomib in combination with gemcitabine and carboplatin in advanced non-small cell lung cancer: a California Cancer Consortium Phase I study. J Thorac Oncol 3:68–74PubMedGoogle Scholar
  25. 25.
    Yang J, Amiri KI, Burke JR et al (2006) BMS-345541 targets inhibitor of kappaB kinase and induces apoptosis in melanoma: involvement of nuclear factor kappaB and mitochondria pathways. Clin Cancer Res 12:950–960PubMedCrossRefGoogle Scholar
  26. 26.
    Lam LT, Davis RE, Pierce J et al (2005) Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling. Clin Cancer Res 11:28–40PubMedCrossRefGoogle Scholar
  27. 27.
    Cilloni D, Messa F, Arruga F et al (2006) The NF-kappaB pathway blockade by the IKK inhibitor PS1145 can overcome imatinib resistance. Leukemia 20:61–67PubMedCrossRefGoogle Scholar
  28. 28.
    Yemelyanov A, Gasparian A, Lindholm P et al (2006) Effects of IKK inhibitor PS1145 on NF-kappaB function, proliferation, apoptosis and invasion activity in prostate carcinoma cells. Oncogene 25:387–389PubMedGoogle Scholar

Copyright information

© Feseo 2008

Authors and Affiliations

  • María Cortés Sempere
    • 1
  • Vanesa Rodríguez Fanjul
    • 1
  • Isabel Sánchez Pérez
    • 1
  • Rosario Perona
    • 1
  1. 1.Translational Oncology Unit Centro de Investigación Biomédica en Red para Enfermedades RarasInstituto de Investigaciones Biomédicas CSIC/UAMMadridSpain

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