References
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi:https://doi.org/10.3322/caac.21492.
- Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–132. doi:https://doi.org/10.3322/caac.21338.
- Engel LS, Chow WH, Vaughan TL, Gammon MD, Risch HA, Stanford JL, et al. Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst. 2003;95(18):1404–1413. doi:https://doi.org/10.1093/jnci/djg047.
- Deng H, Shi H, Chen L, Zhou Y, Jiang J. Over-expression of Nectin-4 promotes progression of esophageal cancer and correlates with poor prognosis of the patients. Cancer Cell Int. 2019;19:106. doi:https://doi.org/10.1186/s12935-019-0824-z.
- Tew WP, Kelsen DP, Ilson DH. Targeted therapies for esophageal cancer. Oncologist. 2005;10(8):590–601. doi:https://doi.org/10.1634/theoncologist.10-8-590.
- Chen LJ, Sun J, Wu HY, Zhou SM, Tan Y, Tan M, et al. B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma. Cancer Immunol Immunother. 2011;60(7):1047–1055. doi:https://doi.org/10.1007/s00262-011-1017-3.
- Zeki SS, Bergman JJ, Dunn JM. Endoscopic management of dysplasia and early oesophageal cancer. Best Pract Res Clin Gastroenterol. 2018;36–37:27–36. doi:https://doi.org/10.1016/j.bpg.2018.11.003.
- Yang YM, Hong P, Xu WW, He QY, Li B. Advances in targeted therapy for esophageal cancer. Signal Transduct Target Ther. 2020;5(1):229. doi:https://doi.org/10.1038/s41392-020-00323-3.
- Deeney JT, Belkina AC, Shirihai OS, Corkey BE, Denis GV. BET bromodomain proteins Brd2, Brd3 and Brd4 selectively regulate metabolic pathways in the pancreatic β-cell. PLOS One. 2016;11(3):e0151329. doi:https://doi.org/10.1371/journal.pone.0151329.
- Marazzi I, Greenbaum BD, Low DHP, Guccione E. Chromatin dependencies in cancer and inflammation. Nat Rev Mol Cell Biol. 2018;19(4):245–261. doi:https://doi.org/10.1038/nrm.2017.113.
- Barrero MJ. Epigenetic strategies to boost cancer immunotherapies. Int J Mol Sci. 2017;18(6):1108. doi:https://doi.org/10.3390/ijms18061108.
- Prinjha R, Tarakhovsky A. Chromatin targeting drugs in cancer and immunity. Genes Dev. 2013;27(16):1731–1738. doi:https://doi.org/10.1101/gad.221895.113.
- Perez-Salvia M, Esteller M. Bromodomain inhibitors and cancer therapy: from structures to applications. Epigenetics. 2017;12(5):323–339. doi:https://doi.org/10.1080/15592294.2016.1265710.
- Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer. 2012;12(7):465–477. doi:https://doi.org/10.1038/nrc3256.
- Wu SY, Chiang CM. The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem. 2007;282(18):13141–13145. doi:https://doi.org/10.1074/jbc.R700001200.
- Chen R, Yik JH, Lew QJ, Chao SH. Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer. Biomed Res Int. 2014;2014:232870. doi:https://doi.org/10.1155/2014/232870.
- Noguchi-Yachide T. BET bromodomain as a target of epigenetic therapy. Chem Pharm Bull. 2016;64(6):540–547. doi:https://doi.org/10.1248/cpb.c16-00225.
- Muller S, Filippakopoulos P, Knapp S. Bromodomains as therapeutic targets. Expert Rev Mol Med. 2011;13:e29. doi:https://doi.org/10.1017/S1462399411001992.
- Sakaguchi T, Yoshino H, Sugita S, Miyamoto K, Yonemori M, Osako Y, et al. Bromodomain protein BRD4 inhibitor JQ1 regulates potential prognostic molecules in advanced renal cell carcinoma. Oncotarget. 2018;9(33):23003–23017. doi:https://doi.org/10.18632/oncotarget.25190.
- Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, et al. Selective inhibition of BET bromodomains. Nature. 2010;468(7327):1067–1073. doi:https://doi.org/10.1038/nature09504.
- Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011;478(7370):524–528. doi:https://doi.org/10.1038/nature10334.
- Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI, et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature. 2011;478(7370):529–533. doi:https://doi.org/10.1038/nature10509.
- Shimamura T, Chen Z, Soucheray M, Carretero J, Kikuchi E, Tchaicha JH, et al. Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer. Clin Cancer Res. 2013;19(22):6183–6192. doi:https://doi.org/10.1158/1078-0432.CCR-12-3904.
- Segura MF, Fontanals-Cirera B, Gaziel-Sovran A, Guijarro MV, Hanniford D, Zhang G, et al. BRD4 sustains melanoma proliferation and represents a new target for epigenetic therapy. Cancer Res. 2013;73(20):6264–6276. doi:https://doi.org/10.1158/0008-5472.CAN-13-0122-T.
- Sahai V, Kumar K, Knab LM, Chow CR, Raza SS, Bentrem DJ, et al. BET bromodomain inhibitors block growth of pancreatic cancer cells in three-dimensional collagen. Mol Cancer Ther. 2014;13(7):1907–1917. doi:https://doi.org/10.1158/1535-7163.MCT-13-0925.
- Ceribelli M, Kelly PN, Shaffer AL, Wright GW, Xiao W, Yang Y, et al. Blockade of oncogenic IκB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. Proc Natl Acad Sci USA. 2014;111(31):11365–11370. doi:https://doi.org/10.1073/pnas.1411701111.
- Asangani IA, Dommeti VL, Wang X, Malik R, Cieslik M, Yang R, et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014;510(7504):278–282. doi:https://doi.org/10.1038/nature13229.
- Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, et al. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature. 2016;529(7586):413–417. doi:https://doi.org/10.1038/nature16508.
- Garcia PL, Miller AL, Kreitzburg KM, Council LN, Gamblin TL, Christein JD, et al. The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016;35(7):833–845. doi:https://doi.org/10.1038/onc.2015.126.
- Hu Y, Zhou J, Ye F, Xiong H, Peng L, Zheng Z, et al. BRD4 inhibitor inhibits colorectal cancer growth and metastasis. Int J Mol Sci. 2015;16(1):1928–1948. doi:https://doi.org/10.3390/ijms16011928.
- Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci USA. 2011;108(40):16669–16674. doi:https://doi.org/10.1073/pnas.1108190108.
- Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146(6):904–917. doi:https://doi.org/10.1016/j.cell.2011.08.017.
- Wang J, Liu Z, Wang Z, Wang S, Chen Z, Li Z, et al. Targeting c-Myc: JQ1 as a promising option for c-Myc-amplified esophageal squamous cell carcinoma. Cancer Lett. 2018;419:64–74. doi:https://doi.org/10.1016/j.canlet.2018.01.051.
- Xu JL, Yuan YJ, Lv J, Qi D, Wu MD, Lan J, et al. Inhibition of BRD4 triggers cellular senescence through suppressing aurora kinases in oesophageal cancer cells. J Cell Mol Med. 2020;24(22):13036–13045. doi:https://doi.org/10.1111/jcmm.15901.
- Hammes LS, Tekmal RR, Naud P, Edelweiss MI, Kirma N, Valente PT, et al. Up-regulation of VEGF, c-fms and COX-2 expression correlates with severity of cervical cancer precursor (CIN) lesions and invasive disease. Gynecol Oncol. 2008;110(3):445–451. doi:https://doi.org/10.1016/j.ygyno.2008.04.038.
- Detre S, Saclani Jotti G, Dowsett M. A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 1995;48(9):876–878. doi:https://doi.org/10.1136/jcp.48.9.876.
- Rustgi AK, El-Serag HB. Esophageal carcinoma. N Engl J Med. 2014;371(26):2499–2509. doi:https://doi.org/10.1056/NEJMra1314530.
- Chang S, Kohrt H, Maecker HT. Monitoring the immune competence of cancer patients to predict outcome. Cancer Immunol Immunother. 2014;63(7):713–719. doi:https://doi.org/10.1007/s00262-014-1521-3.
- Chen JG, Chen HZ, Zhu J, Yang YL, Zhang YH, Huang PX, et al. Cancer survival in patients from a hospital-based cancer registry, China. J Cancer. 2018;9(5):851–860. doi:https://doi.org/10.7150/jca.23039.
- Li GQ, Guo WZ, Zhang Y, Seng JJ, Zhang HP, Ma XX, et al. Suppression of BRD4 inhibits human hepatocellular carcinoma by repressing MYC and enhancing BIM expression. Oncotarget. 2016;7(3):2462–2474. doi:https://doi.org/10.18632/oncotarget.6275.
- Xiang T, Bai JY, She C, Yu DJ, Zhou XZ, Zhao TL. Bromodomain protein BRD4 promotes cell proliferation in skin squamous cell carcinoma. Cell Signal. 2018;42:106–113. doi:https://doi.org/10.1016/j.cellsig.2017.10.010.
- Sakamaki J-I, Wilkinson S, Hahn M, Tasdemir N, O'Prey J, Clark W, et al. Bromodomain protein BRD4 is a transcriptional repressor of autophagy and lysosomal function. Mol Cell. 2017;66(4):517–532.e9. doi:https://doi.org/10.1016/j.molcel.2017.04.027.
- Zhang C, Su ZY, Wang L, Shu L, Yang Y, Guo Y, et al. Epigenetic blockade of neoplastic transformation by bromodomain and extra-terminal (BET) domain protein inhibitor JQ-1. Biochem Pharmacol. 2016;117:35–45. doi:https://doi.org/10.1016/j.bcp.2016.08.009.
- White ME, Fenger JM, Carson WE III. Emerging roles of and therapeutic strategies targeting BRD4 in cancer. Cell Immunol. 2019;337:48–53. doi:https://doi.org/10.1016/j.cellimm.2019.02.001.
- Wu X, Liu D, Tao D, Xiang W, Xiao X, Wang M, et al. BRD4 regulates EZH2 transcription through upregulation of C-MYC and represents a novel therapeutic target in bladder cancer. Mol Cancer Ther. 2016;15(5):1029–1042. doi:https://doi.org/10.1158/1535-7163.MCT-15-0750.
- Rhyasen GW, Yao Y, Zhang J, Dulak A, Castriotta L, Jacques K, et al. BRD4 amplification facilitates an oncogenic gene expression program in high-grade serous ovarian cancer and confers sensitivity to BET inhibitors. PLOS One. 2018;13(7):e0200826. doi:https://doi.org/10.1371/journal.pone.0200826.
- Mochizuki K, Nishiyama A, Jang MK, Dey A, Ghosh A, Tamura T, et al. The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase. J Biol Chem. 2008;283(14):9040–9048. doi:https://doi.org/10.1074/jbc.M707603200.
- Yang Z, He N, Zhou Q. Brd4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression and cell cycle progression. Mol Cell Biol. 2008;28(3):967–976. doi:https://doi.org/10.1128/MCB.01020-07.
- Itzen F, Greifenberg AK, Bosken CA, Geyer M. Brd4 activates P-TEFb for RNA polymerase II CTD phosphorylation. Nucleic Acids Res. 2014;42(12):7577–7590. doi:https://doi.org/10.1093/nar/gku449.
- Andrieu GP, Shafran JS, Deeney JT, Bharadwaj KR, Rangarajan A, Denis GV. BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment. J Leukoc Biol. 2018;104(2):265–274. doi:https://doi.org/10.1002/JLB.5RI0917-380RR.
- Zhu H, Bengsch F, Svoronos N, Rutkowski MR, Bitler BG, Allegrezza MJ, et al. BET bromodomain inhibition promotes anti-tumor immunity by suppressing PD-L1 expression. Cell Rep. 2016;16(11):2829–2837. doi:https://doi.org/10.1016/j.celrep.2016.08.032.
- Andrikopoulou A, Liontos M, Koutsoukos K, Dimopoulos M-A, Zagouri F. The emerging role of BET inhibitors in breast cancer. Breast. 2020;53:152–163. doi:https://doi.org/10.1016/j.breast.2020.08.005.
- Duan Y, Guan Y, Qin W, Zhai X, Yu B, Liu H. Targeting Brd4 for cancer therapy: inhibitors and degraders. Medchemcomm. 2018;9(11):1779–1802. doi:https://doi.org/10.1039/c8md00198g.
- Wu X, Liu D, Gao X, Xie F, Tao D, Xiao X, et al. Inhibition of BRD4 suppresses cell proliferation and induces apoptosis in renal cell carcinoma. Cell Physiol Biochem. 2017;41(5):1947–1956. doi:https://doi.org/10.1159/000472407.
- Tan Y, Wang L, Du Y, Liu X, Chen Z, Weng X, et al. Inhibition of BRD4 suppresses tumor growth in prostate cancer via the enhancement of FOXO1 expression. Int J Oncol. 2018;53(6):2503–2517. doi:https://doi.org/10.3892/ijo.2018.4577.
- French CA. Small-molecule targeting of BET proteins in cancer. Adv Cancer Res. 2016;131:21–58.
- Leal AS, Williams CR, Royce DB, Pioli PA, Sporn MB, Liby KT. Bromodomain inhibitors, JQ1 and I-BET 762, as potential therapies for pancreatic cancer. Cancer Lett. 2017;394:76–87. doi:https://doi.org/10.1016/j.canlet.2017.02.021.
- Andrews FH, Singh AR, Joshi S, Smith CA, Morales GA, Garlich JR, et al. Dual-activity PI3K-BRD4 inhibitor for the orthogonal inhibition of MYC to block tumor growth and metastasis. Proc Natl Acad Sci USA. 2017;114(7):E1072–E1080. doi:https://doi.org/10.1073/pnas.1613091114.
- Donati B, Lorenzini E, Ciarrocchi A. BRD4 and Cancer: going beyond transcriptional regulation. Mol Cancer. 2018;17(1):164. doi:https://doi.org/10.1186/s12943-018-0915-9.
- Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, et al. Super-enhancers in the control of cell identity and disease. Cell. 2013;155(4):934–947. doi:https://doi.org/10.1016/j.cell.2013.09.053.
- Zhang P, Dong Z, Cai J, Zhang C, Shen Z, Ke A, et al. BRD4 promotes tumor growth and epithelial-mesenchymal transition in hepatocellular carcinoma. Int J Immunopathol Pharmacol. 2015;28(1):36–44. doi:https://doi.org/10.1177/0394632015572070.
- Zhou X, Cui Z, Liu Y, Yue Z, Xie F, Ding L, et al. Correlation of bromodomain protein BRD4 expression with epithelial-mesenchymal transition and disease severity in chronic rhinosinusitis with nasal polyps. Front Med. 2020;7:413. doi:https://doi.org/10.3389/fmed.2020.00413.
- Tan Y-F, Wang M, Chen Z-Y, Wang L, Liu X-H. Inhibition of BRD4 prevents proliferation and epithelial-mesenchymal transition in renal cell carcinoma via NLRP3 inflammasome-induced pyroptosis. Cell Death Dis. 2020;11(4):239. doi:https://doi.org/10.1038/s41419-020-2431-2.