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NF-κB as potential target in the treatment of melanoma

By Gabriele Madonna, Claudio Dansky Ullman, Giusy Gentilcore, Giuseppe Palmieri and Paolo Antonio Ascierto

Abstract

The RAS/MAP kinase pathway has attracted attention because activating mutations of the BRAF serine/threonine kinase was described in over 50% of melanomas. Very recently, selective and potent BRAF inhibitors have been developed. Several other signal transduction pathways have been found to be constitutively active or mutated in other subsets of melanoma tumors that are potentially targetable with new agents. Among these, NFκB is another pathway that melanoma tumors use to achieve survival, proliferation and resistance to apoptosis. Inhibition of NF-κB activation appears to be a very promising option for anti-cancer therapies

Topics: Review
Publisher: BioMed Central
OAI identifier: oai:pubmedcentral.nih.gov:3338086
Provided by: PubMed Central
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    Citations

    1. (2002). A: A novel NF-kappa B-inducing kinase-MAPK signaling pathway up-regulates NF-kappa B activity in melanoma cells.
    2. (2004). A: Augmenting chemosensitivity of malignant melanoma tumors via proteasome inhibition: Implication for bortezomib (VELCADE, PS-341) as a therapeutic agent for malignant melanoma. Cancer Res
    3. (2006). A: BMS-345541 Targets Inhibitor of κB Kinase and Induces Apoptosis in Melanoma: Involvement of Nuclear Factor κB and Mitochondria Pathways. Clin Cancer Res
    4. (2004). A: Effect of curcumin on gelatinase A (MMP-2) activity in B16F10 melanoma cells. Cancer Lett
    5. (1997). A: Enhanced Degradation of I-κBα Contributes to Endogenous Activation of NF-κB in Hs294T Melanoma Cells. Cancer Res
    6. (2001). Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science
    7. (2003). AR: Identification of a nuclear factor κ B-dependent gene network. Recent Prog Horm Res
    8. (2009). Ascierto PA: Main roads to melanoma.
    9. (2003). Bharti AC: Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res
    10. (2002). Characterization of the IκB-kinase NEMO binding domain.
    11. (2001). Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB.
    12. (2010). Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer
    13. (2011). DE: A new era: melanoma genetics and therapeutics.
    14. (2006). DE: Dose escalation of a curcuminoid formulation.
    15. (2002). Debs RJ: Identification of gene function and functional pathways by systemic plasmid-based ribozyme targeting in adult mice.
    16. (2000). Delhase M: The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling. Semin Immunol
    17. (2008). E: Doubleblind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group. J Clin Oncol
    18. (2007). Fuchs SY: Oncogenic BRAF regulates β-Trcp expression and NF-κB activity in human melanoma cells. Oncogene
    19. (2011). GA: BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation.
    20. (2009). GB: Curcumin induces proapoptotic effects against human melanoma cells and modulates the cellular response to immunotherapeutic cytokines. Cancer Res
    21. (2009). Ialenti A: NEMObinding domain peptide inhibits proliferation of human melanoma cells. Cancer Lett
    22. (2001). Issues in the epidemiology of melanoma. Expert Rev Anticancer Ther
    23. (2005). Kundu GC: Osteopontin: It’s Role in Regulation of Cell Motility and Nuclear Factor kB-mediated Urokinase Type Plasminogen activator Expression. IUBMB Life
    24. (2004). Madoulet C: In vitro and in vivo anti-tumoral effect of curcumin against melanoma cells.
    25. (2010). Melanoma: a model for testing new agents in combination therapies.
    26. (2002). Missing pieces in the NF-κB puzzle. Cell
    27. (2008). Modulation of antiapoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells. Biochem Pharmacol
    28. (2005). Osteopontin Expression Correlates with Melanoma Invasion.
    29. (2008). Phase III, open-label, randomized, comparative study of tremelimumab (CP-675,206) and chemotherapy (temozolomide [TMZ] or dacarbazine [DTIC]) in patients with advanced melanoma.
    30. (2000). Phosphorylation meets ubiquitination: the control of NF-κB activity. Ann Rev Immunol
    31. (2005). S: Amelioration of acute inflammation by systemic administration of a cell-permeable peptide inhibitor of NF-κB activation. Arthritis and Rheumatism
    32. (2000). Selective inhibition of NFκB activation by a peptide that blocks the interaction of NEMO with the IκB-kinase complex. Science
    33. (2010). Sosman JA: A phase I trial of bortezomib with temozolomide in patients with advanced melanoma: toxicities, antitumor effects, and modulation of therapeutic targets. Clin Cancer Res
    34. (2004). The proteasome: a suitable antineoplastic target. Nat Rev Cancer
    35. (2009). U: Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma.
    36. (2010). Urba WJ: Improved survival with ipilimumab in patients with metastatic melanoma.
    37. (2006). V: Genetic alterations in signaling pathways in melanoma. Clin Cancer Res
    38. (2004). Yang S: Comparative expression of NFKB proteins in melanocytes of normal skin vs benign intradermal naevus and human metastatic melanoma biopsies. Pigment Cell Res
    39. (2003). Zusi FC: BMS-345541 is a highly selective inhibitor of IκB kinase that binds at an allosteric site of the enzyme and blocks NF-κB-dependent transcription in mice.

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