Page 31 - GTM-2-3

Global Translational Medicine Critical roles for BRD4 identified in cancer

44. Ledermann JA, Harter P, Gourley C, et al., 2016, Overall controls transcriptional elongation of inflammatory
survival in patients with platinum-sensitive recurrent cytokines in respiratory syncytial virus infection. J Virol,
serous ovarian cancer receiving olaparib maintenance 85: 11752–11769.
monotherapy: An updated analysis from a randomised, https://doi.org/10.1128/JVI.05360-11
placebo-controlled, double-blind, phase 2 trial. Lancet
Oncol, 17: 1579–1589. 55. Zou Z, Huang B, Wu X, et al., 2014, Brd4 maintains
constitutively active NF-κB in cancer cells by binding to
https://doi.org/10.1016/S1470-2045(16)30376-X
acetylated RelA. Oncogene, 33: 2395–2404.
45. Ledermann JA, Harter P, Gourley C, et al., 2016, Overall https://doi.org/10.1038/onc.2013.179
survival (OS) in patients (pts) with platinum-sensitive
relapsed serous ovarian cancer (PSR SOC) receiving 56. Lee H, Herrmann A, Deng JH, et al., 2009, Persistently
olaparib maintenance monotherapy: An interim analysis. activated Stat3 maintains constitutive NF-kappaB activity in
J Clin Oncol, 34: 5501. tumors. Cancer Cell, 15: 283–293.
https://doi.org/10.1200/JCO.2016.34.15_suppl.5501 https://doi.org/10.1016/j.ccr.2009.02.015
46. Zimmer AS, Gillard M, Lipkowitz S, et al., 2018, Update on 57. Levy D, Kuo AJ, Chang Y, et al., 2011, Lysine methylation
PARP inhibitors in breast cancer. Curr Treat Options Oncol, of the NF-κB subunit RelA by SETD6 couples activity of
19: 21. the histone methyltransferase GLP at chromatin to tonic
repression of NF-κB signaling. Nat Immunol, 12: 29–36.
https://doi.org/10.1007/s11864-018-0540-2
https://doi.org/10.1038/ni.1968
47. Sun CY, Yin J, Fang Y, et al., 2018, BRD4 inhibition is
synthetic lethal with PARP inhibitors through the induction 58. Chapuy B, McKeown MR, Lin CY, et al., 2013, Discovery and
of homologous recombination deficiency. Cancer Cell, characterization of super-enhancer-associated dependencies
33: 401–416.e8. in diffuse large B cell lymphoma. Cancer Cell, 24: 777–790.
https://doi.org/10.1016/j.ccell.2018.01.019 https://doi.org/10.1016/j.ccr.2013.11.003
48. Donati B, Lorenzini E, Ciarrocchi A, 2018, BRD4 and 59. Delmore JE, Issa GC, Lemieux ME, et al., 2011, BET
cancer: Going beyond transcriptional regulation. Mol bromodomain inhibition as a therapeutic strategy to target
Cancer, 17: 164. c-Myc. Cell, 146: 904–917.
https://doi.org/10.1186/s12943-018-0915-9 https://doi.org/10.1016/j.cell.2011.08.017
49. Gee ME, Faraahi Z, McCormick A, et al., 2018, DNA damage 60. Gröschel S, Sanders MA, Hoogenboezem R, et al., 2014,
repair in ovarian cancer: Unlocking the heterogeneity. A single oncogenic enhancer rearrangement causes
J Ovarian Res, 11: 50. concomitant EVI1 and GATA2 deregulation in leukemia.
Cell, 157: 369–381.
https://doi.org/10.1186/s13048-018-0424-x
https://doi.org/10.1016/j.cell.2014.02.019
50. Dey A, Chitsaz F, Abbasi A, et al., 2003, The double
bromodomain protein Brd4 binds to acetylated chromatin 61. Glodzik D, Morganella S, Davies H, et al., 2017, A somatic-
during interphase and mitosis. Proc Natl Acad Sci U S A, mutational process recurrently duplicates germline
100: 8758–8763. susceptibility loci and tissue-specific super-enhancers in
breast cancers. Nat Genet, 49: 341–348.
https://doi.org/10.1073/pnas.1433065100
https://doi.org/10.1038/ng.3771
51. Choi S, Bakkenist CJ, 2013, Brd4 shields chromatin from
ATM kinase signaling storms. Sci Signal, 6: pe30. 62. Dang CV, O’Donnell KA, Zeller KI, et al., 2006, The c-Myc
target gene network. Semin Cancer Biol, 16: 253–264.
https://doi.org/10.1126/scisignal.2004622
https://doi.org/10.1016/j.semcancer.2006.07.014
52. Rodriguez RM, Huidobro C, Urdinguio RG, et al., 2012,
Aberrant epigenetic regulation of bromodomain BRD4 in 63. Filippakopoulos P, Qi J, Picaud S, et al., 2010, Selective
human colon cancer. J Mol Med (Berl), 90: 587–595. inhibition of BET bromodomains. Nature, 468: 1067–1073.
https://doi.org/10.1007/s00109-011-0837-0 https://doi.org/10.1038/nature09504
53. Filippakopoulos P, Knapp S, 2014, Targeting bromodomains: 64. Nicodeme E, Jeffrey KL, Schaefer U, et al., 2010, Suppression
Epigenetic readers of lysine acetylation. Nat Rev Drug of inflammation by a synthetic histone mimic. Nature,
Discov, 13: 337–356. 468: 1119–1123.
https://doi.org/10.1038/nrd4286 https://doi.org/10.1038/nature09589
54. Brasier AR, Tian B, Jamaluddin M, et al., 2011, RelA 65. Mertz JA, Conery AR, Bryant BM, et al., 2011, Targeting MYC
Ser276 phosphorylation-coupled Lys310 acetylation dependence in cancer by inhibiting BET bromodomains.

Volume 2 Issue 3 (2023) 10 https://doi.org/10.36922/gtm.1442