REFERENCES
1. Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2016 (GBD 2016) Results [Institute for Health Metrics and Evaluation (IHME), 2017]. Available from https://www.who.int/news-room/fact-sheets/detail/cancer [Last accessed on 20 Mar 2020].
2. Kannaiyan R, Mahadevan D. A comprehensive review of protein kinase inhibitors for cancer therapy. Expert Rev Anticancer Ther 2018;18:1249-70.
3. Roskoski R Jr. Properties of FDA-approved small molecule protein kinase inhibitors: a 2020 update. Pharmacol Res 2020;152:104609.
4. Colomer C, Margalef P, Villanueva A, Vert A, Pecharroman I, et al. IKKα kinase regulates the DNA damage response and drives chemo-resistance in cancer. Mol Cell 2019;75:669-82.e5.
5. Roseweir AK, Bennett L, Dickson A, Cheng K, Quintayo MA, et al. Predictive biomarkers for endocrine therapy: retrospective study in tamoxifen and exemestane adjuvant multinational (TEAM) trial. J Natl Cancer Inst 2018;110:616-27.
6. Colomer C, Marruecos L, Vert A, Bigas A, Espinosa L. NF-κB members left home: NF-κB-independent roles in cancer. Biomedicines 2017;5:26.
7. Régnier CH, Song HY, Gao X, Goeddel DV, Cao Z, et al. Identification and characterization of an IκB kinase. Cell 1997;90:373-83.
8. Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell 1997;91:243-52.
9. Häcker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE 2006;2006:re13.
10. Mercurio F. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-B activation. Science 1997;278:860-6.
11. Hinz M, Scheidereit C. The IκB kinase complex in NF-κB regulation and beyond. EMBO Rep 2014;15:46-61.
12. Gilmore TD, Herscovitch M. Inhibitors of NF-κB signaling: 785 and counting. Oncogene 2006;25:6887-99.
13. Gilmore TD, Garbati MR. Inhibition of NF-κB signaling as a strategy in disease therapy. Curr Top Microbiol Immunol 2011;349:245-63.
14. Karin M, Yamamoto Y, Wang QM. The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov 2004;3:17-26.
15. Prescott J, Cook S. Targeting IKKβ in cancer: challenges and opportunities for the therapeutic utilisation of IKKβ inhibitors. Cells 2018;7:115.
16. Chariot A. The NF-kappaB-independent functions of IKK subunits in immunity and cancer. Trends Cell Biol 2009;19:404-13.
17. Margalef P, Fernández-Majada V, Villanueva A, Garcia-Carbonell R, Iglesias M, et al. A truncated form of IKKα is responsible for specific nuclear IKK activity in colorectal cancer. Cell Rep 2012;2:840-54.
18. Zhu F, Xia X, Liu B, Shen J, Hu Y, et al. IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing. Mol Cell 2007;27:214-27.
19. Fernández-Majada V, Aguilera C, Villanueva A, Vilardell F, Robert-Moreno A, et al. Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer. Proc Natl Acad Sci U S A 2007;104:276-81.
20. Fernández-Majada V, Pujadas J, Vilardell F, Capella G, Mayo MW, et al. Aberrant cytoplasmic localization of N-CoR in colorectal tumors. Cell Cycle 2007;6:1748-52.
21. Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, et al. A nucleosomal function for IκB kinase-α in NF-κB-dependent gene expression. Nature 2003;423:659-63.
22. Hoberg JE, Yeung F, Mayo MW. SMRT derepression by the IkappaB kinase alpha: a prerequisite to NF-kappaB transcription and survival. Mol Cell 2004;16:245-55.
23. Albanese C, Wu K, D’Amico M, Jarrett C, Joyce D, et al. IKKalpha regulates mitogenic signaling through transcriptional induction of cyclin D1 via Tcf. Mol Biol Cell 2003;14:585-99.
24. Marinari B, Moretti F, Botti E, Giustizieri ML, Descargues P, et al. The tumor suppressor activity of IKKalpha in stratified epithelia is exerted in part via the TGF-beta antiproliferative pathway. Proc Natl Acad Sci U S A 2008;105:17091-6.
25. Descargues P, Sil AK, Sano Y, Korchynskyi O, Han G, et al. IKKalpha is a critical coregulator of a Smad4-independent TGFbeta-Smad2/3 signaling pathway that controls keratinocyte differentiation. Proc Natl Acad Sci U S A 2008;105:2487-92.
26. Alameda JP, Gaspar M, Ramírez Á, Navarro M, Page A, et al. Deciphering the role of nuclear and cytoplasmic IKKα in skin cancer. Oncotarget 2016;7:29531-47.
27. Vreka M, Lilis I, Papageorgopoulou M, Giotopoulou GA, Lianou M, et al. IkB kinase a is required for development and progression of KRAS-mutant lung adenocarcinoma. Cancer Res 2018;78:2939-51.
28. Ducut Sigala JL, Bottero V, Young DB, Shevchenko A, Mercurio F, et al. Activation of transcription factor NF-κB requires ELKS, an IkappaB kinase regulatory subunit. Science 2004;304:1963-7.
29. Cao Y, Luo JL, Karin M. IkappaB kinase alpha kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells. Proc Natl Acad Sci U S A 2007;104:15852-7.
30. Jia J, Shi Y, Yan B, Xiao D, Lai W, et al. LGR5 expression is controled by IKKα in basal cell carcinoma through activating STAT3 signaling pathway. Oncotarget 2016;7:27280-94.
31. Colomer C, Margalef P, Gonzalez J, Vert A, Bigas A, et al. IKKα is required in the intestinal epithelial cells for tumour stemness. Br J Cancer 2018;118:839-46.
32. Mulero MC, Ferres-Marco D, Islam A, Margalef P, Pecoraro M, et al. Chromatin-bound IκBα regulates a subset of polycomb target genes in differentiation and cancer. Cancer Cell 2013;24:151-66.
33. Fernández-Majada V, Aguilera C, Villanueva A, Vilardell F, Robert-Moreno A, et al. Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer. Proc Natl Acad Sci U S A 2007;104:276-81.
34. Margalef P, Colomer C, Villanueva A, Montagut C, Iglesias M, et al. BRAF-induced tumorigenesis is IKKα-dependent but NF-κB-independent. Sci Signal 2015;8:ra38.
35. Luo JL, Tan W, Ricono JM, Korchynskyi O, Zhang M, et al. Nuclear cytokine-activated IKKα controls prostate cancer metastasis by repressing Maspin. Nature 2007;446:690-4.
36. Ammirante M, Luo JL, Grivennikov S, Nedospasov S, Karin M. B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature 2010;464:302-5.
37. Toll A, Margalef P, Masferrer E, Ferrándiz-Pulido C, Gimeno J, et al. Active nuclear IKK correlates with metastatic risk in cutaneous squamous cell carcinoma. Arch Dermatol Res 2015;307:721-9.
38. Page A, Ortega A, Alameda JP, Navarro M, Paramio JM, et al. IKKα promotes the progression and metastasis of non-small cell lung cancer independently of its subcellular localization. Comput Struct Biotechnol J 2019;17:251-62.
39. Gonzalez-Suarez E, Jacob AP, Jones J, Miller R, Roudier-Meyer MP, et al. RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis. Nature 2010;468:103-7.
40. Schramek D, Leibbrandt A, Sigl V, Kenner L, Pospisilik JA, et al. Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature 2010;468:98-102.
41. Tan W, Zhang W, Strasner A, Grivennikov S, Cheng JQ, et al. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 2011;470:548-53.
42. Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, et al. Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by I kappa B kinase. Mol Cell Biol 2002;22:3549-61.
43. Park KJ, Krishnan V, O’Malley BW, Yamamoto Y, Gaynor RB. Formation of an IKKα-dependent transcription complex is required for estrogen receptor-mediated gene activation. Mol Cell 2005;18:71-82.
44. Bennett L, Quinn J, McCall P, Mallon EA, Horgan PG, et al. High IKKα expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)-positive breast cancer. Int J Cancer 2017;140:1633-644.
45. Hossain F, Sorrentino C, Ucar DA, Peng Y, Matossian M, et al. Notch signaling regulates mitochondrial metabolism and NF-κB activity in triple-negative breast cancer cells via IKKα-dependent non-canonical pathways. Front Oncol 2018;8:575.
46. Folmer F, Jaspars M, Dicato M, Diederich M. Marine natural products as targeted modulators of the transcription factor NF-kappaB. Biochem Pharmacol 2008;75:603-17.
47. Ríos JL, Recio MC, Escandell JM, Andújar I. Inhibition of transcription factors by plant-derived compounds and their implications in inflammation and cancer. Curr Pharm Des 2009;15:1212-37.
48. Castro AC, Dang LC, Soucy F, Grenier L, Mazdiyasni H, et al. Novel IKK inhibitors: β-carbolines. Bioorg Med Chem Lett 2003;13:2419-22.
49. Habineza Ndikuyeze G, Gaurnier-Hausser A, Patel R, Baldwin AS, et al. A phase I clinical trial of systemically delivered NEMO binding domain peptide in dogs with spontaneous activated B-cell like diffuse large B-cell lymphoma. PLoS One 2014;9:e95404.
50. Lee DF, Hung MC. Advances in targeting IKK and IKK-related kinases for cancer therapy. Clin Cancer Res 2008;14:5656-62.
51. Shukla S, Kanwal R, Shankar E, Datt M, Chance MR, et al. Apigenin blocks IKKα activation and suppresses prostate cancer progression. Oncotarget 2015;6:31216-32.
52. Leopizzi M, Cocchiola R, Milanetti E, Raimondo D, Politi L, et al. IKKα inibition by a glucosamine derivative enhances Maspin expression in osteosarcoma cell line. Chem Biol Interact 2017;262:19-28.
53. Anthony NG, Baiget J, Berretta G, Boyd M, Breen D, et al. Inhibitory kappa B kinase α (IKKα) inhibitors that recapitulate their selectivity in cells against isoform-related biomarkers. J Med Chem 2017;60:7043-66.
54. Lam LT, Davis RE, Pierce J, Hepperle M, Xu Y, et al. 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 2005;11:28-40.
55. Schön M, Wienrich BG, Kneitz S, Sennefelder H, Amschler K, et al. KINK-1, a novel small-molecule inhibitor of IKKβ, and the susceptibility of melanoma cells to antitumoral treatment. J Natl Cancer Inst 2008;100:862-75.
56. Dai L, Aye Thu C, Liu XY, Xi J, Cheung PC. TAK1, more than just innate immunity. IUBMB Life 2012;64:825-34.
57. Sakurai H, Shigemori N, Hasegawa K, Sugita T. TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism. Biochem Biophys Res Commun 1998;243:545-9.
