REFERENCES
1. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, et al. Drug resistance in cancer: an overview. Cancers (Basel). 2014;6:1769-92.
2. Lage H. An overview of cancer multidrug resistance: a still unsolved problem. Cell Mol Life Sci. 2008;65:3145-67.
3. Hu X, Zhang Z. Understanding the Genetic Mechanisms of Cancer Drug Resistance Using Genomic Approaches. Trends Genet. 2016;32:127-37.
5. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2002;2:48-58.
8. Swanton C. Intratumor heterogeneity: evolution through space and time. Cancer Res. 2012;72:4875-82.
9. Taylor ST, Hickman JA, Dive C. Epigenetic determinants of resistance to etoposide regulation of Bcl-X(L) and Bax by tumor microenvironmental factors. J Natl Cancer Inst. 2000;92:18-23.
10. Valent P, Bonnet D, De Maria R, Lapidot T, Copland M, et al. Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer. 2012;12:767-75.
11. Lee TI, Young RA. Transcriptional regulation and its misregulation in disease. Cell. 2013;152:1237-51.
13. Kohno K, Uchiumi T, Niina I, Wakasugi T, Igarashi T, et al. Transcription factors and drug resistance. Eur J Cancer. 2005;41:2577-86.
14. Zou W, Ma X, Yang H, Hua W, Chen B, et al. Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer. Exp Biol Med. 2017;242:497-504.
15. Uchida Y, Itoh M, Taguchi Y, Yamaoka S, Umehara H, et al. Ceramide Reduction and Transcriptional Up-Regulation of Glucosylceramide Synthase through Doxorubicin-Activated Sp1 in Drug-Resistant HL-60/ADR Cells. Cancer Res. 2004;64:6271-9.
16. Mo D, Fang H, Niu K, Liu J, Wu M, et al. Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT-YB1-MDR1 Signaling Pathway. Cancer Res. 2016;76:3057-66.
17. Yan XY, Zhang Y, Zhang JJ, Zhang LC, Liu YN, et al. p62/SQSTM1 as an oncotarget mediates cisplatin resistance through activating RIP1-NF-κB pathway in human ovarian cancer cells. Cancer Sci. 2017;108:1405-13.
18. Bao L, Wu J, Dodson M, Rojo de la Vega EM, Ning Y, et al. ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells. Mol Carcinog. 2017;56:1543-53.
19. Shibata T, Kokubu A, Gotoh M, Ojima H, Ohta T, et al. Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer. Gastroenterology. 2008;135:1358-68, 68 e1-4.
20. Jiang T, Chen N, Zhao F, Wang XJ, Kong B, et al. High levels of Nrf2 determine chemoresistance in type II endometrial cancer. Cancer Res. 2010;70:5486-96.
21. Ren D, Villeneuve NF, Jiang T, Wu T, Lau A, et al. Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism. Proc Natl Acad Sci U S A. 2011;108:1433-8.
22. Xiang Y, Ye W, Huang C, Yu D, Chen H, et al. Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway. Oxid Med Cell Longev. 2018;2018:2360427.
23. Wang XJ, Sun Z, Villeneuve NF, Zhang S, Zhao F, et al. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis. 2008;29:1235-43.
24. Tarumoto T, Nagai T, Ohmine K, Miyoshi T, Nakamura M, et al. Ascorbic acid restores sensitivity to imatinib via suppression of Nrf2-dependent gene expression in the imatinib-resistant cell line. Exp Hematol. 2004;32:375-81.
25. Kim SK, Yang JW, Kim MR, Roh SH, Kim HG, et al. Increased expression of Nrf2/ARE-dependent anti-oxidant proteins in tamoxifen-resistant breast cancer cells. Free Radic Biol Med. 2008;45:537-46.
26. Khalil HS, Langdon SP, Goltsov A, Soininen T, Harrison DJ, et al. A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells. Oncotarget. 2016;7:75874-901.
27. Kankia IH, Khalil HS, Langdon SP, Moult PR, Bown JL, et al. NRF2 Regulates HER1 Signaling Pathway to Modulate the Sensitivity of Ovarian Cancer Cells to Lapatinib and Erlotinib. Oxid Med Cell Longev. 2017;2017:1864578.
28. Park SH, Kim JH, Ko E, Kim JY, Park MJ, et al. Resistance to gefitinib and cross-resistance to irreversible EGFR-TKIs mediated by disruption of the Keap1-Nrf2 pathway in human lung cancer cells. FASEB J. 2018; doi: 10.1096/fj.201800011R. [Epub ahead of print]
29. Pei S, Minhajuddin M, D’Alessandro A, Nemkov T, Stevens BM, et al. Rational Design of a Parthenolide-based Drug Regimen That Selectively Eradicates Acute Myelogenous Leukemia Stem Cells. J Biol Chem. 2016;291:21984-2000.
30. Nawijn MC, Alendar A, Berns A. For better or for worse: the role of Pim oncogenes in tumorigenesis. Nat Rev Cancer. 2011;11:23-34.
31. Li B, Fu J, Chen P, Ge X, Li Y, et al. The Nuclear Factor (Erythroid-derived 2)-like 2 and Proteasome Maturation Protein Axis Mediate Bortezomib Resistance in Multiple Myeloma. J Biol Chem. 2015;290:29854-68.
32. Shiozawa K, Oka M, Soda H, Yoshikawa M, Ikegami Y, et al. Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic. Int J Cancer. 2004;108:146-51.
33. Robey RW, Medina-Perez WY, Nishiyama K, Lahusen T, Miyake K, et al. Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin Cancer Res. 2001;7:145-52.
34. Nagashima S, Soda H, Oka M, Kitazaki T, Shiozawa K, et al. BCRP/ABCG2 levels account for the resistance to topoisomerase I inhibitors and reversal effects by gefitinib in non-small cell lung cancer. Cancer Chemother Pharmacol. 2006;58:594-600.
35. Bai X, Chen Y, Hou X, Huang M, Jin J. Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters. Drug Metab Rev. 2016;48:541-67.
36. Chen F, Zhuang M, Zhong C, Peng J, Wang X, et al. Baicalein reverses hypoxia-induced 5-FU resistance in gastric cancer AGS cells through suppression of glycolysis and the PTEN/Akt/HIF-1alpha signaling pathway. Oncol Rep. 2015;33:457-63.
37. Leone A, Roca MS, Ciardiello C, Terranova-Barberio M, Vitagliano C, et al. Vorinostat synergizes with EGFR inhibitors in NSCLC cells by increasing ROS via up-regulation of the major mitochondrial porin VDAC1 and modulation of the c-Myc-NRF2-KEAP1 pathway. Free Radical Bio Med. 2015;89:287-99.
38. Li M, Wu X, Liu N, Li X, Meng F, et al. Silencing of ATF2 inhibits growth of pancreatic cancer cells and enhances sensitivity to chemotherapy. Cell Biol Int. 2017;41:599-610.
39. Wakasugi T, Izumi H, Uchiumi T, Suzuki H, Arao T, et al. ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes. Oncogene. 2007;26:5194.
40. Mohler J, Mahaffey JW, Deutsch E, Vani K. Control of Drosophila head segment identity by the bZIP homeotic gene cnc. Development. 1995;121:237-47.
41. Chan JY, Han XL, Kan YW. Isolation of cDNA encoding the human NF-E2 protein. Proc Natl Acad Sci U S A. 1993;90:11366-70.
42. Chan JY, Han XL, Kan YW. Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proc Natl Acad Sci U S A. 1993;90:11371-5.
43. Moi P, Chan K, Asunis I, Cao A, Kan YW. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A. 1994;91:9926-30.
44. Itoh K, Igarashi K, Hayashi N, Nishizawa M, Yamamoto M. Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins. Mol Cell Biol. 1995;15:4184-93.
45. Kobayashi A, Ito E, Toki T, Kogame K, Takahashi S, et al. Molecular cloning and functional characterization of a new Cap’n’collar family transcription factor Nrf3. J Biol Chem. 1999;274:6443-52.
46. Oyake T, Itoh K, Motohashi H, Hayashi N, Hoshino H, et al. Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site. Mol Cell Biol. 1996;16:6083-95.
47. Muto A, Hoshino H, Madisen L, Yanai N, Obinata M, et al. Identification of Bach2 as a B-cell-specific partner for small Maf proteins that negatively regulate the immunoglobulin heavy chain gene 3ʹ enhancer. EMBO J. 1998;17:5734-43.
48. Igarashi K, Kataokat K, Itoh K, Hayashi N, Nishizawa M, et al. Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature. 1994;367:568-72.
49. Igarashi K, Hoshino H, Muto A, Suwabe N, Nishikawa S, et al. Multivalent DNA binding complex generated by small Maf and Bach1 as a possible biochemical basis for β-globin locus control region complex. J Biol Chem. 1998;273:11783-90.
50. Itoh K. An Nrf2/small Maf heterodimer mediates the induction of Phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997;236:313-22.
51. Hayes JD, Ebisine K, Sharma RS, Chowdhry S, Dinkova-Kostova AT, et al. Regulation of the CNC-bZIP transcription factor Nrf2 by Keap1 and the axis between GSK-3 and β-TrCP. Curr Opin Toxicolog. 2016;1:92-103.
52. O’Mealey GB, Berry WL, Plafker SM. Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission. Redox Biology. 2017;11:103-10.
53. Ahmed SMU, Luo L, Namani A, Wang XJ, Tang X. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis. 2017;1863:585-97.
54. Namani A, Li Y, Wang XJ, Tang X. Modulation of NRF2 signaling pathway by nuclear receptors: Implications for cancer. Biochim Biophys Acta. 2014;1843:1875-85.
55. Wang XJ, Hayes JD, Henderson CJ, Wolf CR. Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Proc Natl Acad Sci U S A. 2007;104:19589-94.
56. Hayes AJ, Skouras C, Haugk B, Charnley RM. Keap1-Nrf2 signalling in pancreatic cancer. Int J Biochem Cell Biol. 2015;65:288-99.
57. Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39:199-218.
58. McMahon M, Campbell KH, MacLeod AK, McLaughlin LA, Henderson CJ, et al. HDAC Inhibitors Increase NRF2-Signaling in Tumour Cells and Blunt the Efficacy of Co-Adminstered Cytotoxic Agents. PLoS ONE. 2014;9:e114055.
59. Hayes JD, McMahon M, Chowdhry S, Dinkova-Kostova AT. Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathway. Antioxid Redox Signal. 2010;13:1713-48.
60. Krajka-Kuźniak V, Paluszczak J, Baer-Dubowska W. The Nrf2-ARE signaling pathway: An update on its regulation and possible role in cancer prevention and treatment. Pharmacol Rep. 2017;69:393-402.
61. Huang HC, Nguyen T, Pickett CB. Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2. Proc Natl Acad Sci U S A. 2000;97:12475-80.
62. Nguyen T, Sherratt PJ, Huang HC, Yang CS, Pickett CB. Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element Degradation of Nrf2 by the 26 S proteasome. J Biol Chem. 2003;278:4536-41.
63. Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol. 2013;53:401-26.
64. Hayes John D, Ashford Michael LJ. Nrf2 Orchestrates Fuel Partitioning for Cell Proliferation. Cell Metab. 2012;16:139-41.
65. Hayes JD. The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin. Biochem Soc Trans. 2000;28:33-41.
66. Krajka-Kuźniak V, Paluszczak J, Baer-Dubowska W. The Nrf2-ARE signaling pathway: an update on its regulation and possible role in cancer prevention and treatment. Pharmacol Rep. 2016; doi: 10.1016/j.pharep.2016.12.011.
67. Xiang M, Namani A, Wu S, Wang X. Nrf2: bane or blessing in cancer? J Cancer Res Clin Oncol. 2014;140:1251-9.
68. Cullinan SB, Diehl JA. PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem. 2004;279:20108-17.
69. Lewis KN, Mele J, Hayes JD, Buffenstein R. Nrf2, a guardian of healthspan and gatekeeper of species longevity. Integr Comp Biol. 2010;50:829-43.
70. Bruns DR, Drake JC, Biela LM, Peelor FF, Miller BF, et al. Nrf2 Signaling and the Slowed Aging Phenotype: Evidence from Long-Lived Models. Oxid Med Cell Longev. 2015;2015:732596.
71. Singh SP, Niemczyk M, Saini D, Sadovov V, Zimniak L, et al. Disruption of the mGsta4 gene increases life span of C57BL mice. J Gerontol A Biol Sci Med Sci. 2010;65:14-23.
72. Sykiotis GP, Bohmann D. Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila. Dev Cell. 2008;14:76-85.
73. Praslicka BJ, Kerins MJ, Ooi A. The complex role of NRF2 in cancer: A genomic view. Curr Opin Toxicolog. 2016;1:37-45.
74. Ramos-Gomez M, Kwak MK, Dolan PM, Itoh K, Yamamoto M, et al. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci U S A. 2001;98:3410-5.
75. Pearson KJ, Lewis KN, Price NL, Chang JW, Perez E, et al. Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction. Proc Natl Acad Sci U S A. 2008;105:2325-30.
76. Padmanabhan B, Tong KI, Ohta T, Nakamura Y, Scharlock M, et al. Structural Basis for Defects of Keap1 Activity Provoked by Its Point Mutations in Lung Cancer. Mol Cell. 2006;21:689-700.
77. Singh A. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med. 2006;3:e420.
78. Solis LM, Behrens C, Dong W, Suraokar M, Ozburn NC, et al. Nrf2 and Keap1 Abnormalities in Non-Small Cell Lung Carcinoma and Association with Clinicopathologic Features. Clin Cancer Res. 2010;16:3743-53.
79. Lignitto L, LeBoeuf SE, Homer H, Jiang S, Askenazi M, et al. Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1. Cell. 2019;178:316-29e18.
80. Wu J, Wang H, Tang X. Rexinoid inhibits Nrf2-mediated transcription through retinoid X receptor alpha. Biochem Biophys Res Commun. 2014;452:554-9.
81. Chorley BN, Campbell MR, Wang X, Karaca M, Sambandan D, et al. Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha. Nucleic Acids Res. 2012;40:7416-29.
82. Khalil HS, Langdon SP, Kankia IH, Bown J, Deeni YY. NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies. Oxid Med Cell Longev. 2016; doi: 10.1155/2016/4148791.
83. Khalil H, Deeni Y. NRF2 inhibition causes repression of ATM and ATR expression leading to aberrant DNA Damage Response. BioDiscovery. 2015;15:1.
84. Khalil HS, Langdon SP, Goltsov A, Soininen T, Harrison DJ, et al. A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells. Oncotarget. 2016;7:75874-901.
85. Hayes JD, McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci. 2009;34:176-88.
86. Yen WC, Corpuz MR, Prudente RY, Cooke TA, Bissonnette RP, et al. A Selective Retinoid X Receptor Agonist Bexarotene (Targretin) Prevents and Overcomes Acquired Paclitaxel (Taxol) Resistance in Human Non-Small Cell Lung Cancer. Clin Cancer Res. 2004;10:8656-64.
87. Yen WC, Prudente RY, Lamph WW. Synergistic effect of a retinoid X receptor-selective ligand bexarotene (LGD1069, Targretin) and paclitaxel (Taxol) in mammary carcinoma. Breast Cancer Res Tr. 2004;88:141-8.
88. Yen WC, Lamph WW. A selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced prostate cancer. Prostate. 2006;66:305-16.
89. Olayanju A, Copple IM, Bryan HK, Edge GT, Sison RL, et al. Brusatol provokes a rapid and transient inhibition of Nrf2 signaling and sensitizes mammalian cells to chemical toxicity—implications for therapeutic targeting of Nrf2. Free Radical Bio Med. 2015;78:202-12.
90. Ren D, Villeneuve NF, Jiang T, Wu T, Lau A, et al. Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism. Proc Natl Acad Sci U S A. 2011;108:1433-8.
91. Chian S, Thapa R, Chi Z, Wang XJ, Tang X. Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo. Biochem Biophys Res Commun. 2014;447:602-8.
92. Tang X, Wang H, Fan L, Wu X, Xin A, et al. Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs. Free Radical Bio Med. 2011;50:1599-609.
93. Gao AM, Ke ZP, Shi F, Sun GC, Chen H. Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway. Chem Biol Interact. 2013;206:100-8.
94. Gao AM, Ke ZP, Wang JN, Yang JY, Chen SY, et al. Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway. Carcinogenesis. 2013;34:1806-14.
96. Na HK, Kim EH, Jung JH, Lee HH, Hyun JW, et al. (−)-Epigallocatechin gallate induces Nrf2-mediated antioxidant enzyme expression via activation of PI3K and ERK in human mammary epithelial cells. Arch Biochem Biophys. 2008;476:171-7.
97. Kim SK, Yang JW, Kim MR, Roh SH, Kim HG, et al. Increased expression of Nrf2/ARE-dependent anti-oxidant proteins in tamoxifen-resistant breast cancer cells. Free Radical Bio Med. 2008;45:537-46.
98. Li W, Yu S, Liu T, Kim JH, Blank V, et al. Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif. Biochim Biophys Acta. 2008;1783:1847-56.
99. Kim SJ, Kim JM, Shim SH, Chang HI. Anthocyanins accelerate the healing of naproxen-induced gastric ulcer in rats by activating antioxidant enzymes via modulation of Nrf2. J Funct Foods. 2014;7:569-79.
100. Kim I, He YY. Ultraviolet radiation-induced non-melanoma skin cancer: Regulation of DNA damage repair and inflammation. Genes Dis. 2014;1:188-98.
101. Thimmulappa RK, Mai KH, Srisuma S, Kensler TW, Yamamoto M, et al. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res. 2002;62:5196-203.
102. Kwak MK, Itoh K, Yamamoto M, Kensler TW. Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: role of antioxidant response element-like sequences in the nrf2 promoter. Mol Cell Biol. 2002;22:2883-92.
103. Lee JS, Surh YJ. Nrf2 as a novel molecular target for chemoprevention. Cancer lett. 2005;224:171-84.
105. Kensler TW, Wakabayashi N. Nrf2: friend or foe for chemoprevention? Carcinogenesis. 2010;31:90-9.
106. Sarkar FH.
107. Ahn YH, Hwang Y, Liu H, Wang XJ, Zhang Y, et al. Electrophilic tuning of the chemoprotective natural product sulforaphane. Proc Natl Acad Sci U S A. 2010;107:9590-5.
108. Talalay P, Fahey JW, Healy ZR, Wehage SL, Benedict AL, et al. Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation. Proc Natl Acad Sci U S A. 2007;104:17500-5.
109. Dietz BM, Kang YH, Liu G, Eggler AL, Yao P, et al. Xanthohumol isolated from Humulus lupulus inhibits menadione-induced DNA damage through induction of quinone reductase. Chem Res Toxicol. 2005;18:1296-305.
110. Lee IS, Lim J, Gal J, Kang JC, Kim HJ, et al. Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochem Int. 2011;58:153-60.
111. Balogun E, Hoque M, Pengfei G, Killeen E, Green CJ, et al. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J. 2003;371:887-95.
112. Farombi EO, Shrotriya S, Na HK, Kim SH, Surh YJ. Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1. Food Chem Toxicol. 2008;46:1279-87.
113. Rushworth SA, Ogborne RM, Charalambos CA, O’Connell MA. Role of protein kinase C δ in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochem Biophys Res Commun. 2006;341:1007-16.
114. Clarke JD, Dashwood RH, Ho E. Multi-targeted prevention of cancer by sulforaphane. Cancer lett. 2008;269:291-304.
115. Iida K. Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis. Cancer Res. 2004;64:6424-31.
116. Stefanson AL, Bakovic M. Dietary regulation of Keap1/Nrf2/ARE pathway: focus on plant-derived compounds and trace minerals. Nutrients. 2014;6:3777-801.
117. Jones RM, Desai C, Darby TM, Luo L, Wolfarth AA, et al. Lactobacilli Modulate Epithelial Cytoprotection through the Nrf2 Pathway. Cell Rep. 2015;12:1217-25.
118. Hamada T, Nowak JA, Milner DA, Song M, Ogino S. Integration of microbiology, molecular pathology, and epidemiology: a new paradigm to explore the pathogenesis of microbiome-driven neoplasms. J Pathol. 2019;247:615-28.
119. Shuji O, Jonathan AN, Tsuyoshi H, Danny AM, Reiko N. Insights into Pathogenic Interactions Among Environment, Host, and Tumor at the Crossroads of Molecular Pathology and Epidemiology. Annu Rev Pathol-Mech. 2019;14:83-103.
120. Kwak MK, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M, et al. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway Identification of novel gene clusters for cell survival. J Biol Chem. 2003;278:8135-45.
121. Cho JM, Manandhar S, Lee HR, Park HM, Kwak MK. Role of the Nrf2-antioxidant system in cytotoxicity mediated by anticancer cisplatin: Implication to cancer cell resistance. Cancer Lett. 2008;260:96-108.
122. Wang XJ. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis. 2008;29:1235-43.
123. Goldstein Leonard D, Lee J, Gnad F, Klijn C, Schaub A, et al. Recurrent Loss of NFE2L2 Exon 2 Is a Mechanism for Nrf2 Pathway Activation in Human Cancers. Cell Rep. 2016;16:2605-17.
124. Wu Q, Yao B, Li N, Ma L, Deng Y, et al. Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells. Exp Cell Res. 2017;352:245-54.
125. Tsuchida K, Tsujita T, Hayashi M, Ojima A, Keleku-Lukwete N, et al. Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation. Free Radical Bio Med. 2017;103:236-47.
126. Kim SK, Kim H, Lee DH, Kim TS, Kim T, et al. Reversing the intractable nature of pancreatic cancer by selectively targeting ALDH-high, therapy-resistant cancer cells. PLoS One. 2013;8:e78130.
127. Sporn MB, Liby KT. NRF2 and cancer: the good, the bad and the importance of context. Nat Rev Cancer. 2012;12:564-71.
128. Ryoo IG, Ha H, Kwak MK. Inhibitory role of the KEAP1-NRF2 pathway in TGFβ1-stimulated renal epithelial transition to fibroblastic cells: a modulatory effect on SMAD signaling. PloS one. 2014;9:e93265.
129. Ooi A, Wong JC, Petillo D, Roossien D, Perrier-Trudova V, et al. An Antioxidant Response Phenotype Shared between Hereditary and Sporadic Type 2 Papillary Renal Cell Carcinoma. Cancer Cell. 2011;20:511-23.
130. DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu Z, et al. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet. 2015;47:1475-81.
131. Ishikawa T. Genetic polymorphism in the NRF2 gene as a prognosis marker for cancer chemotherapy. Front Genet. 2014;5:383.
132. Hartikainen JM, Tengström M, Kosma VM, Kinnula VL, Mannermaa A, et al. Genetic Polymorphisms and Protein Expression of NRF2 and Sulfiredoxin Predict Survival Outcomes in Breast Cancer. Cancer Res. 2012;72:5537-46.
133. Cho HY, Jedlicka AE, Gladwell W, Marzec J, McCaw ZR, et al. Association of Nrf2 polymorphism haplotypes with acute lung injury phenotypes in inbred strains of mice. Antioxid Redox Signal. 2015;22:325-38.
134. Ge W, Zhao K, Wang X, Li H, Yu M, et al. iASPP Is an Antioxidative Factor and Drives Cancer Growth and Drug Resistance by Competing with Nrf2 for Keap1 Binding. Cancer Cell. 2017;32:561-73.e6.
135. Lau A, Wang XJ, Zhao F, Villeneuve NF, Wu T, et al. A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62. Mol Cell Biol. 2010;30:3275-85.
136. Chen W, Sun Z, Wang XJ, Jiang T, Huang Z, et al. Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. Mol Cell. 2009;34:663-73.
137. Wang B, Zhu X, Kim Y, Li J, Huang S, et al. Histone deacetylase inhibition activates transcription factor Nrf2 and protects against cerebral ischemic damage. Free RadicaL Bio Med. 2012;52:928-36.
138. Ji L, Li H, Gao P, Shang G, Zhang DD, et al. Nrf2 pathway regulates multidrug-resistance-associated protein 1 in small cell lung cancer. PLoS One. 2013;8:e63404.
139. Dinkova-Kostova AT, Talalay P. NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector. Arch Biochem Biophys. 2010;501:116-23.
140. Zhong Y, Zhang F, Sun Z, Zhou W, Li ZY, et al. Drug resistance associates with activation of Nrf2 in MCF-7/DOX cells, and wogonin reverses it by down-regulating Nrf2-mediated cellular defense response. Mol Carcinogen. 2013;52:824-34.
141. Hou X, Bai X, Gou X, Zeng H, Xia C, et al. 3’,4’,5’,5,7-pentamethoxyflavone sensitizes Cisplatin-resistant A549 cells to Cisplatin by inhibition of Nrf2 pathway. Mol Cells. 2015;38:396-401.
142. Duong HQ, Yi YW, Kang HJ, Hong YB, Tang W, et al. Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. Int J Oncol. 2013;44:959-69.
143. Chian S, Li YY, Wang XJ, Tang XW. Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway. Asian Pac J Cancer Prev. 2014;15:2911-6.
144. Beall HD, Winski SI. Mechanisms of action of quinone-containing alkylating agents. I: NQO1-directed drug development. Front Biosci. 2000;5:D639-48.
145. Zhu Z, Mu Y, Qi C, Wang J, Xi G, et al. CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro. Int J Mol Med. 2015;35:340-8.
146. Rochat B, Morsman JM, Murray GI, Figg WD, McLeod HL. Human CYP1B1 and Anticancer Agent Metabolism: Mechanism for Tumor-Specific Drug Inactivation? J Pharmacol Exp Ther. 2001;296:537-41.
147. Nebert DW, Wikvall K, Miller WL. Human cytochromes P450 in health and disease. Philos Trans R Soc Lond B Biol Sci. 2013;368:20120431.
148. McFadyen MCE, McLeod HL, Jackson FC, Melvin WT, Doehmer J, et al. Cytochrome P450 CYP1B1 protein expression:: A novel mechanism of anticancer drug resistance11Abbreviations: CYP, cytochrome P450; ANF, alpha-naphthoflavone; MTT, 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide; and 5-FU, 5-fluorouracil. Biochem Pharmacol. 2001;62:207-12.
149. Ax W, Soldan M, Koch L, Maser E. Development of daunorubicin resistance in tumour cells by induction of carbonyl reduction. Biochem Pharmacol. 2000;59:293-300.
150. Gonzalez B, Akman S, Doroshow J, Rivera H, Kaplan WD, et al. Protection against Daunorubicin Cytotoxicity by Expression of a Cloned Human Carbonyl Reductase cDNA in K562 Leukemia Cells. Cancer Res. 1995;55:4646-50.
151. Ikeda R, Vermeulen LC, Lau E, Jiang Z, Sachidanandam K, et al. Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells. Int J Oncol. 2011;38:513-9.
152. Matsunaga T, Yamane Y, Iida K, Endo S, Banno Y, et al. Involvement of the aldo-keto reductase, AKR1B10, in mitomycin-c resistance through reactive oxygen species-dependent mechanisms. Anticancer Drugs. 2011;22:402-8.
153. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51-88.
154. Noda E, Maeda K, Inoue T, Fukunaga S, Nagahara H, et al. Predictive value of expression of ERCC 1 and GST-p for 5-fluorouracil/oxaliplatin chemotherapy in advanced colorectal cancer. Hepatogastroenterology. 2012;59:130-3.
155. Romero-Lorca A, Novillo A, Gaibar M, Bandres F, Fernandez-Santander A. Impacts of the Glucuronidase Genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 on Tamoxifen Metabolism in Breast Cancer Patients. PLoS One. 2015;10:e0132269.
156. Scotlandi K, Remondini D, Castellani G, Manara MC, Nardi F, et al. Overcoming resistance to conventional drugs in Ewing sarcoma and identification of molecular predictors of outcome. J Clin Oncol. 2009;27:2209-16.
157. Bachas S, Eginton C, Gunio D, Wade H. Structural contributions to multidrug recognition in the multidrug resistance (MDR) gene regulator, BmrR. Proc Natl Acad Sci U S A. 2011;108:11046-51.
158. Singh A, Wu H, Zhang P, Happel C, Ma J, et al. Expression of ABCG2 (BCRP) is regulated by Nrf2 in cancer cells that confers side population and chemoresistance phenotype. Mol Cancer Ther. 2010;9:2365-76.
159. Stockel B, Konig J, Nies AT, Cui Y, Brom M, et al. Characterization of the 5’-flanking region of the human multidrug resistance protein 2 (MRP2) gene and its regulation in comparison withthe multidrug resistance protein 3 (MRP3) gene. Eur J Biochem. 2000;267:1347-58.
160. Xu S, Weerachayaphorn J, Cai SY, Soroka CJ, Boyer JL. Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression. Am J Physiol Gastrointest Liver Physiol. 2010;299:G126-35.
161. Shim GS, Manandhar S, Shin DH, Kim TH, Kwak MK. Acquisition of doxorubicin resistance in ovarian carcinoma cells accompanies activation of the NRF2 pathway. Free Radical Bio Med. 2009;47:1619-31.
162. Young LC, Campling BG, Cole SPC, Deeley RG, Gerlach JH. Multidrug Resistance Proteins MRP3, MRP1, and MRP2 in Lung Cancer. Clin Cancer Res. 2001;7:1798-804.
163. Halon A, Materna V, Donizy P, Matkowski R, Rabczynski J, et al. MRP2 (ABCC2, cMOAT) expression in nuclear envelope of primary fallopian tube cancer cells is a new unfavorable prognostic factor. Arch Gynecol Obstet. 2013;287:563-70.
164. Materna V, Liedert B, Thomale J, Lage H. Protection of platinum-DNA adduct formation and reversal of cisplatin resistance by anti-MRP2 hammerhead ribozymes in human cancer cells. Int J Cancer. 2005;115:393-402.
165. Choi HK, Yang JW, Roh SH, Han CY, Kang KW. Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells. Endocr Relat Cancer. 2007;14:293-303.
166. Zhang YH, Wu Q, Xiao XY, Li DW, Wang XP. Silencing MRP4 by small interfering RNA reverses acquired DDP resistance of gastric cancer cell. Cancer Lett. 2010;291:76-82.
167. Zhang L, Fang CH, Fan YF. [Detection of multidrug resistance-associated proteins MRP2, MRP3, and MRP5 mRNA expressions in hepatocarcinoma cells using SYBR real-time PCR]. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28:219-21.
168. Gao AM, Ke ZP, Wang JN, Yang JY, Chen SY, et al. Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway. Carcinogenesis. 2013;34:1806-14.
169. Nakanishi T. Drug transporters as targets for cancer chemotherapy. Cancer Genom Proteom. 2007;4:241-54.
170. Huang Y, Sadée W. Membrane transporters and channels in chemoresistance and -sensitivity of tumor cells. Cancer Lett. 2006;239:168-82.
171. Esteras N, Dinkova-Kostova Albena T, Abramov Andrey Y. Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function. In. Biological Chemistry;. 2016:383. (ISBN No. 14316730)
172. Januchowski R, Zawierucha P, Andrzejewska M, Rucinski M, Zabel M. Microarray-based detection and expression analysis of ABC and SLC transporters in drug-resistant ovarian cancer cell lines. Biomed Pharmacother. 2013;67:240-5.
173. Okuno S, Sato H, Kuriyama-Matsumura K, Tamba M, Wang H, et al. Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines. Br J Cancer. 2003;88:951-6.
174. Yin Y, Liu Q, Wang B, Chen G, Xu L, et al. Expression and function of heme oxygenase-1 in human gastric cancer. Exp Biol Med (Maywood). 2012;237:362-71.
175. Jeon WK, Hong HY, Seo WC, Lim KH, Lee HY, et al. Smad7 sensitizes A549 lung cancer cells to cisplatin-induced apoptosis through heme oxygenase-1 inhibition. Biochem Biophys Res Commun. 2012;420:288-92.
176. Heasman SA, Zaitseva L, Bowles KM, Rushworth SA, Macewan DJ. Protection of acute myeloid leukaemia cells from apoptosis induced by front-line chemotherapeutics is mediated by haem oxygenase-1. Oncotarget. 2011;2:658-68.
177. Nagai T, Kikuchi S, Ohmine K, Miyoshi T, Nakamura M, et al. Hemin reduces cellular sensitivity to imatinib and anthracyclins via Nrf2. J Cell Biochem. 2008;104:680-91.
178. Basta PV, Bensen JT, Tse CK, Perou CM, Sullivan PF, et al. Genetic variation in Transaldolase 1 and risk of squamous cell carcinoma of the head and neck. Cancer Detect Prev. 2008;32:200-8.
179. Cui Y, Nadiminty N, Liu C, Lou W, Schwartz CT, et al. Upregulation of glucose metabolism by NF-kappaB2/p52 mediates enzalutamide resistance in castration-resistant prostate cancer cells. Endocr Relat Cancer. 2014;21:435-42.
180. Wang Z, Liang S, Lian X, Liu L, Zhao S, et al. Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis. Sci Rep. 2015;5:9301.
181. Zhang M, Chai YD, Brumbaugh J, Liu X, Rabii R, et al. Oral cancer cells may rewire alternative metabolic pathways to survive from siRNA silencing of metabolic enzymes. BMC Cancer. 2014;14:223.
182. Chen Z, Ye X, Tang N, Shen S, Li Z, et al. The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti-drug responses in human non-small cell lung cancer. Br J Pharmacol. 2014;171:3196-211.
183. Shah NM, Rushworth SA, Murray MY, Bowles KM, MacEwan DJ. Understanding the role of NRF2-regulated miRNAs in human malignancies. Oncotarget. 2013;4:1130-42.
184. Ceppi P, Mudduluru G, Kumarswamy R, Rapa I, Scagliotti GV, et al. Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer. Mol Cancer Res. 2010;8:1207-16.
185. Cochrane DR, Howe EN, Spoelstra NS, Richer JK. Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers. J Oncol. 2010;2010:821717.
186. Liu S, Tetzlaff MT, Cui R, Xu X. miR-200c inhibits melanoma progression and drug resistance through down-regulation of BMI-1. Am J Pathol. 2012;181:1823-35.
187. Lister A, Nedjadi T, Kitteringham NR, Campbell F, Costello E, et al. Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy. Mol cancer. 2011;10:37.
188. Khalil HS, Goltsov A, Langdon SP, Harrison DJ, Bown J, et al. Quantitative analysis of NRF2 pathway reveals key elements of the regulatory circuits underlying antioxidant response and proliferation of ovarian cancer cells. J Biotechnol. 2015;202:12-30.
189. Kweon MH, Adhami VM, Lee JS, Mukhtar H. Constitutive overexpression of Nrf2-dependent heme oxygenase-1 in A549 cells contributes to resistance to apoptosis induced by epigallocatechin 3-gallate. J Biol Chem. 2006;281:33761-72.
190. Jiang T. High levels of Nrf2 determine chemoresistance in type II endometrial cancer. Cancer Res. 2010;70:5486-96.
191. Stacy DR, Ely K, Massion PP, Yarbrough WG, Hallahan DE, et al. Increased expression of nuclear factor E2 p45□related factor 2 (NRF2) in head and neck squamous cell carcinomas. Head Neck. 2006;28:813-8.
192. Kim YS, Lee HL, Lee KB, Park JH, Chung WY, et al. Nuclear factor E2-related factor 2 dependent overexpression of sulfiredoxin and peroxiredoxin III in human lung cancer. Korean J Intern Med. 2011;26:304-13.
193. Ohta T, Iijima K, Miyamoto M, Nakahara I, Tanaka H, et al. Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res. 2008;68:1303-9.
194. Shibata T, Ohta T, Tong KI, Kokubu A, Odogawa R, et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci U S A. 2008;105:13568-73.
195. Pandey P, Singh AK, Singh M, Tewari M, Shukla HS, et al. The see-saw of Keap1-Nrf2 pathway in Cancer. Crit Rev Oncol Hematol. 2017;116:89-98.
196. No JH, Kim YB, Song YS. Targeting Nrf2 Signaling to Combat Chemoresistance. J Cancer. 2014;19:111-7.
197. Petroski MD, Deshaies RJ. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol. 2005;6:9-20.
198. Skaar JR, Pagan JK, Pagano M. Mechanisms and function of substrate recruitment by F-box proteins. Nat Rev Mol Cell Biol. 2013;14:369-81.
199. Chen HY, Chen RH. Cullin 3 Ubiquitin Ligases in Cancer Biology: Functions and Therapeutic Implications. Front Oncol. 2016;6:113.
200. Skaar JR, Pagan JK, Pagano M. SCF ubiquitin ligase-targeted therapies. Nat Rev Drug Discov. 2014;13:889-903.
201. Huang C, Li M, Chen C, Yao Q. Small interfering RNA therapy in cancer: mechanism, potential targets, and clinical applications. Expert Opin Ther Tar. 2008;12:637-45.
202. Guo W, Chen W, Yu W, Huang W, Deng W. Small interfering RNA-based molecular therapy of cancers. Chin J Cancer. 2013;32:488.
203. Kanninen KM, Pomeshchik Y, Leinonen H, Malm T, Koistinaho J, et al. Applications of the Keap1-Nrf2 system for gene and cell therapy. Free Radical Bio Med. 2015;88:350-61.
204. Duong HQ, You KS, Oh S, Kwak SJ, Seong YS. Silencing of NRF2 Reduces the Expression of ALDH1A1 and ALDH3A1 and Sensitizes to 5-FU in Pancreatic Cancer Cells. Antioxidants. 2017;6:52.
205. Esmaeili MA. Combination of siRNA-directed gene silencing with epigallocatechin-3-gallate (EGCG) reverses drug resistance in human breast cancer cells. J Chem Bio. 2016;9:41-52.
206. Curtin NJ. DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer. 2012;12:801-17.
207. Gorrini C, Baniasadi PS, Harris IS, Silvester J, Inoue S, et al. BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival. J Exp Med. 2013;210:1529-44.
208. Kang HJ, Hong YB, Kim HJ, Rodriguez OC, Nath RG, et al. Detoxification: a novel function of BRCA1 in tumor suppression? Toxicol Sci. 2011;122:26-37.
209. Gorrini C, Gang BP, Bassi C, Wakeham A, Baniasadi SP, et al. Estrogen controls the survival of BRCA1-deficient cells via a PI3K-NRF2-regulated pathway. Proc Natl Acad Sci U S A. 2014;111:4472-7.
210. Lee EY, Abbondante S. Tissue-specific tumor suppression by BRCA1. Proc Natl Acad Sci U S A. 2014;111:4353-4.
211. Wu T, Wang XJ, Tian W, Jaramillo MC, Lau A, et al. Poly(ADP-ribose) polymerase-1 modulates Nrf2-dependent transcription. Free Radic Biol Med. 2014;67:69-80.
212. Khalil HS, Deeni Y. NRF2 inhibition causes repression of ATM and ATR expression leading to aberrant DNA Damage Response. BioDiscovery. 2015;15:1.
213. Wang Q, Li J, Yang X, Sun H, Gao S, et al. Nrf2 is associated with the regulation of basal transcription activity of the BRCA1 gene. Acta Biochim Biophys Sin (Shanghai). 2013;45:179-87.
214. Jayakumar S, Pal D, Sandur SK. Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells. Mutat Res. 2015;779:33-45.
215. Rojo de la Vega M, Dodson M, Chapman E, Zhang DD. NRF2-targeted therapeutics: New targets and modes of NRF2 regulation. Curr Opin Toxicol. 2016;1:62-70.
216. Bhullar KS, Lagaron NO, McGowan EM, Parmar I, Jha A, et al. Kinase-targeted cancer therapies: progress, challenges and future directions. Mol Cancer. 2018;17:48.
217. Fabbro D, Ruetz S, Buchdunger E, Cowan-Jacob SW, Fendrich G, et al. Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. Pharmacol Ther. 2002;93:79-98.
218. Mirshafiey A, Ghalamfarsa G, Asghari B, Azizi G. Receptor Tyrosine Kinase and Tyrosine Kinase Inhibitors: New Hope for Success in Multiple Sclerosis Therapy. Innov Clin Neurosci. 2014;11:23-36.
219. Voldborg BR, Damstrup L, Spang-Thomsen M, Poulsen HS. Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann Oncol. 1997;8:1197-206.
220. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127-37.
221. Tzahar E, Yarden Y. The ErbB-2/HER2 oncogenic receptor of adenocarcinomas: from orphanhood to multiple stromal ligands. Biochim Biophys Acta. 1998;1377:M25-37.
222. Hackel PO, Zwick E, Prenzel N, Ullrich A. Epidermal growth factor receptors: critical mediators of multiple receptor pathways. Curr Opin Cell Biol. 1999;11:184-9.
223. Bange J, Zwick E, Ullrich A. Molecular targets for breast cancer therapy and prevention. Nat Med. 2001;7:548-52.
224. Khalil HS, Langdon SP, Kankia IH, Bown J, Deeni YY. NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies. Oxid Med Cell Longev. 2016;2016:4148791.
225. Warfel NA, Sainz AG, Song JH, Kraft AS. PIM Kinase Inhibitors Kill Hypoxic Tumor Cells by Reducing Nrf2 Signaling and Increasing Reactive Oxygen Species. Mol Cancer Ther. 2016;15:1637-47.
226. Duong HQ, Yi YW, Kang HJ, Hong YB, Tang W, et al. Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. Int J Oncol. 2014;44:959-69.
227. Yu R, Lei W, Mandlekar S, Weber MJ, Der CJ, et al. Role of a mitogen-activated protein kinase pathway in the induction of phase II detoxifying enzymes by chemicals. J Biol Chem. 1999;274:27545-52.
228. Yeh CT, Yen GC. Involvement of p38 MAPK and Nrf2 in phenolic acid-induced P-form phenol sulfotransferase expression in human hepatoma HepG2 cells. Carcinogenesis. 2006;27:1008-17.
229. Kang KA, Lee KH, Park JW, Lee NH, Na HK, et al. Triphlorethol-A induces heme oxygenase-1 via activation of ERK and NF-E2 related factor 2 transcription factor. FEBS Lett. 2007;581:2000-8.
230. Zhang H, Liu H, Iles KE, Liu RM, Postlethwait EM, et al. 4-Hydroxynonenal induces rat gamma-glutamyl transpeptidase through mitogen-activated protein kinase-mediated electrophile response element/nuclear factor erythroid 2-related factor 2 signaling. Am J Respir Cell Mol Biol. 2006;34:174-81.
231. Huang H, Wu Y, Fu W, Wang X, Zhou L, et al. Downregulation of Keap1 contributes to poor prognosis and Axitinib resistance of renal cell carcinoma via upregulation of Nrf2 expression. Int J Mol Med. 2019;43:2044-54.
232. Ji S, Xiong Y, Zhao X, Liu Y, Yu LQ. Effect of the Nrf2-ARE signaling pathway on biological characteristics and sensitivity to sunitinib in renal cell carcinoma. Oncol Lett. 2019;17:5175-86.
233. Ma S, Paiboonrungruan C, Yan T, Williams KP, Major MB, et al. Targeted therapy of esophageal squamous cell carcinoma: the NRF2 signaling pathway as target. Ann N Y Acad Sci. 2018;1434:164-72.
234. Tsuchida K, Tsujita T, Hayashi M, Ojima A, Keleku-Lukwete N, et al. Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation. Free Radic Biol Med. 2017;103:236-47.
235. Choi EJ, Jung BJ, Lee SH, Yoo HS, Shin EA, et al. A clinical drug library screen identifies clobetasol propionate as an NRF2 inhibitor with potential therapeutic efficacy in KEAP1 mutant lung cancer. Oncogene. 2017;36:5285.
236. Wu T, Harder BG, Wong PK, Lang JE, Zhang DD. Oxidative stress, mammospheres and Nrf2-new implication for breast cancer therapy? Mol Carcinog. 2015;54:1494-502.
237. Wang H, Liu K, Geng M, Gao P, Wu X, et al. RXRα Inhibits the NRF2-ARE Signaling Pathway through a Direct Interaction with the Neh7 Domain of NRF2. Cancer Res. 2013;73:3097-108.
238. Kang KA, Hyun JW. Oxidative Stress, Nrf2, and Epigenetic Modification Contribute to Anticancer Drug Resistance. Toxicol Res. 2017;33:1-5.
239. Zhang H, Shang YP, Chen HY, Li J. Histone deacetylases function as novel potential therapeutic targets for cancer. Hepatol Res. 2017;47:149-59.
240. Yu JJ, Wu YX, Zhao FJ, Xia SJ. miR-96 promotes cell proliferation and clonogenicity by down-regulating of FOXO1 in prostate cancer cells. Med Oncol. 2014;31:910.
241. Yi TZ, Li J, Han X, Guo J, Qu Q, et al. DNMT inhibitors and HDAC inhibitors regulate E-cadherin and Bcl-2 expression in endometrial carcinoma in vitro and in vivo. Chemotherapy. 2012;58:19-29.
242. Verma M. Cancer control and prevention: nutrition and epigenetics. Curr Opin Clin Nutr Metab Care. 2013;16:376-84.
243. Reichert N, Choukrallah MA, Matthias P. Multiple roles of class I HDACs in proliferation, differentiation, and development. Cell Mol Life Sci. 2012;69:2173-87.
244. Zhang C, Su ZY, Khor TO, Shu L, Kong AN. Sulforaphane enhances Nrf2 expression in prostate cancer TRAMP C1 cells through epigenetic regulation. Biochem Pharmacol. 2013;85:1398-404.
245. Su ZY, Zhang C, Lee JH, Shu L, Wu TY, et al. Requirement and epigenetics reprogramming of Nrf2 in suppression of tumor promoter TPA-induced mouse skin cell transformation by sulforaphane. Cancer Prev Res (Phila). 2014;7:319-29.
246. Hu C, Eggler AL, Mesecar AD, van Breemen RB. Modification of keap1 cysteine residues by sulforaphane. Chem Res Toxicol. 2011;24:515-21.
247. Kensler TW, Egner PA, Agyeman AS, Visvanathan K, Groopman JD, et al. Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane. Top Curr Chem. 2013;329:163-77.
248. Kang KA, Piao MJ, Kim KC, Kang HK, Chang WY, et al. Epigenetic modification of Nrf2 in 5-fluorouracil-resistant colon cancer cells: involvement of TET-dependent DNA demethylation. Cell Death Dis. 2014;5:e1183.
249. Shilatifard A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol. 2008;20:341-8.
250. Khor TO, Huang Y, Wu TY, Shu L, Lee J, et al. Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation. Biochem Pharmacol. 2011;82:1073-8.
251. Paredes-Gonzalez X, Fuentes F, Su ZY, Kong AN. Apigenin reactivates Nrf2 anti-oxidative stress signaling in mouse skin epidermal JB6 P + cells through epigenetics modifications. AAPS J. 2014;16:727-35.
252. Wang L, Zhang C, Guo Y, Su ZY, Yang Y, et al. Blocking of JB6 cell transformation by tanshinone IIA: epigenetic reactivation of Nrf2 antioxidative stress pathway. AAPS J. 2014;16:1214-25.
253. Wu TY, Khor TO, Su ZY, Saw CL, Shu L, et al. Epigenetic modifications of Nrf2 by 3,3’-diindolylmethane in vitro in TRAMP C1 cell line and in vivo TRAMP prostate tumors. AAPS J. 2013;15:864-74.
254. Lee OH, Jain AK, Papusha V, Jaiswal AK. An auto-regulatory loop between stress sensors INrf2 and Nrf2 controls their cellular abundance. J Biol Chem. 2007;282:36412-20.
255. Xu C, Yuan X, Pan Z, Shen G, Kim JH, et al. Mechanism of action of isothiocyanates: the induction of ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2. Mol Cancer Ther. 2006;5:1918-26.
256. Owuor ED, Kong AN. Antioxidants and oxidants regulated signal transduction pathways. Biochem Pharmacol. 2002;64:765-70.
257. Jain A, Lamark T, Sjøttem E, Bowitz Larsen K, Atesoh Awuh J, et al. p62/SQSTM1 Is a Target Gene for Transcription Factor NRF2 and Creates a Positive Feedback Loop by Inducing Antioxidant Response Element-driven Gene Transcription. J Biol Chem. 2010;285:22576-91.
258. Papp D, Lenti K, Módos D, Fazekas D, Dúl Z, et al. The NRF2-related interactome and regulome contain multifunctional proteins and fine-tuned autoregulatory loops. FEBS Lett. 2012;586:1795-802.
