Review Article

基于BRD4的双靶标抑制剂:新型的癌症治疗方法

卷 28, 期 9, 2021

发表于: 10 June, 2020

页: [1775 - 1795] 页: 21

弟呕挨: 10.2174/0929867327666200610174453

价格: $65

摘要

背景:目前,癌症继续对公共健康构成急剧增加和严重的威胁。虽然近年来已经开发出了许多抗肿瘤药物,但患者的存活率并不令人满意。癌症患者的预后差与耐药性的发生密切相关。因此,我们急需制定治疗癌症的新策略。多靶疗法的目的是具有添加剂或协同效应,并通过将不同的药物毒团整合到一个单一的药物分子中,降低耐药性发展的潜力。鉴于大多数疾病在本质上是多因素的,多目标疗法的强度越来越提高,这改善了疾病模型的结果,并获得了几种已进入临床试验的化合物。因此,我们有可能利用这种策略来治疗与BRD4相关的癌症。本文综述了基于BRD4的双靶抑制剂在抗肿瘤方面的最新研究进展。 方法:从在线资源和数据库中检索了有关BRD4抑制剂的文献

关键词: BRD4,抗癌,组合,药物设计,双靶标,酶促/非酶促蛋白。

[1]
Katselou, M.G.; Matralis, A.N.; Kourounakis, A.P. Multi-target drug design approaches for multifactorial diseases: from neurodegenerative to cardiovascular applications. Curr. Med. Chem., 2014, 21(24), 2743-2787.
[http://dx.doi.org/10.2174/0929867321666140303144625] [PMID: 24606519]
[2]
Florence, B.; Faller, D.V. You bet-cha: a novel family of transcriptional regulators. Front. Biosci., 2001, 6(1), D1008-D1018.
[http://dx.doi.org/10.2741/Florence] [PMID: 11487468]
[3]
Donati, B.; Lorenzini, E.; Ciarrocchi, A. BRD4 and cancer: going beyond transcriptional regulation. Mol. Cancer, 2018, 17(1), 164-177.
[http://dx.doi.org/10.1186/s12943-018-0915-9] [PMID: 30466442]
[4]
Dhalluin, C.; Carlson, J.E.; Zeng, L.; He, C.; Aggarwal, A.K.; Zhou, M.M. Structure and ligand of a histone acetyltransferase bromodomain. Nature, 1999, 399(6735), 491-496.
[http://dx.doi.org/10.1038/20974] [PMID: 10365964]
[5]
Wu, S.Y.; Chiang, C.M. The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J. Biol. Chem., 2007, 282(18), 13141-13145.
[http://dx.doi.org/10.1074/jbc.R700001200] [PMID: 17329240]
[6]
Zeng, L.; Zhou, M-M. Bromodomain: an acetyl-lysine binding domain. FEBS Lett., 2002, 513(1), 124-128.
[http://dx.doi.org/10.1016/S0014-5793(01)03309-9] [PMID: 11911891]
[7]
Dey, A.; Ellenberg, J.; Farina, A.; Coleman, A.E.; Maruyama, T.; Sciortino, S.; Lippincott-Schwartz, J.; Ozato, K. A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition. Mol. Cell. Biol., 2000, 20(17), 6537-6549.
[http://dx.doi.org/10.1128/MCB.20.17.6537-6549.2000] [PMID: 10938129]
[8]
Dey, A.; Chitsaz, F.; Abbasi, A.; Misteli, T.; Ozato, K. The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis. Proc. Natl. Acad. Sci. USA, 2003, 100(15), 8758-8763.
[http://dx.doi.org/10.1073/pnas.1433065100] [PMID: 12840145]
[9]
Filippakopoulos, P.; Picaud, S.; Mangos, M.; Keates, T.; Lambert, J.P.; Barsyte-Lovejoy, D.; Felletar, I.; Volkmer, R.; Müller, S.; Pawson, T.; Gingras, A.C.; Arrowsmith, C.H.; Knapp, S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell, 2012, 149(1), 214-231.
[http://dx.doi.org/10.1016/j.cell.2012.02.013] [PMID: 22464331]
[10]
Morinière, J.; Rousseaux, S.; Steuerwald, U.; Soler-López, M.; Curtet, S.; Vitte, A.L.; Govin, J.; Gaucher, J.; Sadoul, K.; Hart, D.J.; Krijgsveld, J.; Khochbin, S.; Müller, C.W.; Petosa, C. Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature, 2009, 461(7264), 664-668.
[http://dx.doi.org/10.1038/nature08397] [PMID: 19794495]
[11]
Shi, J.; Vakoc, C.R. The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol. Cell, 2014, 54(5), 728-736.
[http://dx.doi.org/10.1016/j.molcel.2014.05.016] [PMID: 24905006]
[12]
Ottinger, M.; Christalla, T.; Nathan, K.; Brinkmann, M.M.; Viejo-Borbolla, A.; Schulz, T.F. Kaposi’s sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest. J. Virol., 2006, 80(21), 10772-10786.
[http://dx.doi.org/10.1128/JVI.00804-06] [PMID: 16928766]
[13]
Rahman, S.; Sowa, M.E.; Ottinger, M.; Smith, J.A.; Shi, Y.; Harper, J.W.; Howley, P.M. The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3. Mol. Cell. Biol., 2011, 31(13), 2641-2652.
[http://dx.doi.org/10.1128/MCB.01341-10] [PMID: 21555454]
[14]
Shen, C.; Ipsaro, J.J.; Shi, J.; Milazzo, J.P.; Wang, E.; Roe, J.S.; Suzuki, Y.; Pappin, D.J.; Joshua-Tor, L.; Vakoc, C.R. NSD3-short is an adaptor protein that couples BRD4 to the CHD8 chromatin remodeler. Mol. Cell, 2015, 60(6), 847-859.
[http://dx.doi.org/10.1016/j.molcel.2015.10.033] [PMID: 26626481]
[15]
Chiang, C.M. Phospho-BRD4: transcription plasticity and drug targeting. Drug Discov. Today. Technol., 2016, 19, 17-22.
[http://dx.doi.org/10.1016/j.ddtec.2016.05.003] [PMID: 27769352]
[16]
Wu, S.Y.; Lee, A.Y.; Lai, H.T.; Zhang, H.; Chiang, C.M. Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting. Mol. Cell, 2013, 49(5), 843-857.
[http://dx.doi.org/10.1016/j.molcel.2012.12.006] [PMID: 23317504]
[17]
Korb, E.; Herre, M.; Zucker-Scharff, I.; Darnell, R.B.; Allis, C.D. BET protein Brd4 activates transcription in neurons and BET inhibitor Jq1 blocks memory in mice. Nat. Neurosci., 2015, 18(10), 1464-1473.
[http://dx.doi.org/10.1038/nn.4095] [PMID: 26301327]
[18]
Shu, S.; Lin, C.Y.; He, H.H.; Witwicki, R.M.; Tabassum, D.P.; Roberts, J.M.; Janiszewska, M.; Huh, S.J.; Liang, Y.; Ryan, J.; Doherty, E.; Mohammed, H.; Guo, H.; Stover, D.G.; Ekram, M.B.; Brown, J.; D’Santos, C.; Krop, I.E.; Dillon, D.; McKeown, M.; Ott, C.; Qi, J.; Ni, M.; Rao, P.K.; Duarte, M.; Wu, S.Y.; Chiang, C.M.; Anders, L.; Young, R.A.; Winer, E.; Letai, A.; Barry, W.T.; Carroll, J.S.; Long, H.; Brown, M.; Liu, X.S.; Meyer, C.A.; Bradner, J.E.; Polyak, K. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature, 2016, 529(7586), 413-417.
[http://dx.doi.org/10.1038/nature16508] [PMID: 26735014]
[19]
Alsarraj, J.; Faraji, F.; Geiger, T.R.; Mattaini, K.R.; Williams, M.; Wu, J.; Ha, N.H.; Merlino, T.; Walker, R.C.; Bosley, A.D.; Xiao, Z.; Andresson, T.; Esposito, D.; Smithers, N.; Lugo, D.; Prinjha, R.; Day, A.; Crawford, N.P.; Ozato, K.; Gardner, K.; Hunter, K.W. BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane. PLoS One, 2013, 8(11), e80746.
[http://dx.doi.org/10.1371/journal.pone.0080746] [PMID: 24260471]
[20]
Mochizuki, K.; Nishiyama, A.; Jang, M.K.; Dey, A.; Ghosh, A.; Tamura, T.; Natsume, H.; Yao, H.; Ozato, K. The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase. J. Biol. Chem., 2008, 283(14), 9040-9048.
[http://dx.doi.org/10.1074/jbc.M707603200] [PMID: 18223296]
[21]
Zuber, J.; Shi, J.; Wang, E.; Rappaport, A.R.; Herrmann, H.; Sison, E.A.; Magoon, D.; Qi, J.; Blatt, K.; Wunderlich, M.; Taylor, M.J.; Johns, C.; Chicas, A.; Mulloy, J.C.; Kogan, S.C.; Brown, P.; Valent, P.; Bradner, J.E.; Lowe, S.W.; Vakoc, C.R. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature, 2011, 478(7370), 524-528.
[http://dx.doi.org/10.1038/nature10334] [PMID: 21814200]
[22]
Ember, S.W.; Zhu, J.Y.; Olesen, S.H.; Martin, M.P.; Becker, A.; Berndt, N.; Georg, G.I.; Schönbrunn, E. Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors. ACS Chem. Biol., 2014, 9(5), 1160-1171.
[http://dx.doi.org/10.1021/cb500072z] [PMID: 24568369]
[23]
de Ruijter, A.J.M.; van Gennip, A.H.; Caron, H.N.; Kemp, S. van Kuilenburg. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem. J., 2003, 370(pt 3), 737-749.
[http://dx.doi.org/10.1042/bj20021321] [PMID: 12429021]
[24]
Haberland, M.; Montgomery, R.L.; Olson, E.N. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat. Rev. Genet., 2009, 10(1), 32-42.
[http://dx.doi.org/10.1038/nrg2485] [PMID: 19065135]
[25]
Filippakopoulos, P.; Knapp, S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov., 2014, 13(5), 337-356.
[http://dx.doi.org/10.1038/nrd4286] [PMID: 24751816]
[26]
Bhadury, J.; Nilsson, L.M.; Muralidharan, S.V.; Green, L.C.; Li, Z.; Gesner, E.M.; Hansen, H.C.; Keller, U.B.; McLure, K.G.; Nilsson, J.A. BET and HDAC inhibitors induce similar genes and biological effects and synergize to kill in Myc-induced murine lymphoma. Proc. Natl. Acad. Sci. USA, 2014, 111(26), E2721-E2730.
[http://dx.doi.org/10.1073/pnas.1406722111] [PMID: 24979794]
[27]
Gendarme, M.; Baumann, J.; Ignashkova, T.I.; Lindemann, R.K.; Reiling, J.H. Image-based drug screen identifies HDAC inhibitors as novel Golgi disruptors synergizing with JQ1. Mol. Biol. Cell, 2017, 28(26), 3756-3772.
[http://dx.doi.org/10.1091/mbc.e17-03-0176] [PMID: 29074567]
[28]
Shahbazi, J.; Liu, P.Y.; Atmadibrata, B.; Bradner, J.E.; Marshall, G.M.; Lock, R.B.; Liu, T. The bromodomain inhibitor JQ1 and the histone deacetylase inhibitor panobinostat synergistically reduce N-Myc expression and induce anticancer effects. Clin. Cancer Res., 2016, 22(10), 2534-2544.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1666] [PMID: 26733615]
[29]
Fiskus, W.; Sharma, S.; Qi, J.; Valenta, J.A.; Schaub, L.J.; Shah, B.; Peth, K.; Portier, B.P.; Rodriguez, M.; Devaraj, S.G.; Zhan, M.; Sheng, J.; Iyer, S.P.; Bradner, J.E.; Bhalla, K.N. Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol. Cancer Ther., 2014, 13(5), 1142-1154.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0770] [PMID: 24435446]
[30]
Mazur, P.K.; Herner, A.; Mello, S.S.; Wirth, M.; Hausmann, S.; Sánchez-Rivera, F.J.; Lofgren, S.M.; Kuschma, T.; Hahn, S.A.; Vangala, D.; Trajkovic-Arsic, M.; Gupta, A.; Heid, I.; Noël, P.B.; Braren, R.; Erkan, M.; Kleeff, J.; Sipos, B.; Sayles, L.C.; Heikenwalder, M.; Heßmann, E.; Ellenrieder, V.; Esposito, I.; Jacks, T.; Bradner, J.E.; Khatri, P.; Sweet-Cordero, E.A.; Attardi, L.D.; Schmid, R.M.; Schneider, G.; Sage, J.; Siveke, J.T. Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Nat. Med., 2015, 21(10), 1163-1171.
[http://dx.doi.org/10.1038/nm.3952] [PMID: 26390243]
[31]
Hölscher, A.S.; Schulz, W.A.; Pinkerneil, M.; Niegisch, G.; Hoffmann, M.J. Combined inhibition of BET proteins and class I HDACs synergistically induces apoptosis in urothelial carcinoma cell lines. Clin. Epigenetics, 2018, 10(1), 1-14.
[http://dx.doi.org/10.1186/s13148-017-0434-3] [PMID: 29312470]
[32]
Heinemann, A.; Cullinane, C.; De Paoli-Iseppi, R.; Wilmott, J.S.; Gunatilake, D.; Madore, J.; Strbenac, D.; Yang, J.Y.; Gowrishankar, K.; Tiffen, J.C.; Prinjha, R.K.; Smithers, N.; McArthur, G.A.; Hersey, P.; Gallagher, S.J. Combining BET and HDAC inhibitors synergistically induces apoptosis of melanoma and suppresses AKT and YAP signaling. Oncotarget, 2015, 6(25), 21507-21521.
[http://dx.doi.org/10.18632/oncotarget.4242] [PMID: 26087189]
[33]
Zhang, Y.; Ishida, C.T.; Ishida, W.; Lo, S-L.; Zhao, J.; Shu, C.; Bianchetti, E.; Kleiner, G.; Sanchez-Quintero, M.J.; Quinzii, C.M.; Westhoff, M.A.; Karpel-Massler, G.; Canoll, P.; Siegelin, M.D. Combined HDAC and bromodomain protein inhibition reprograms tumor cell metabolism and elicits synthetic lethality in glioblastoma. Clin. Cancer Res., 2018, 24(16), 3941-3954.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0260] [PMID: 29764852]
[34]
Pinz, S.; Unser, S.; Buob, D.; Fischer, P.; Jobst, B.; Rascle, A. Deacetylase inhibitors repress STAT5-mediated transcription by interfering with bromodomain and extra-terminal (BET) protein function. Nucleic Acids Res., 2015, 43(7), 3524-3545.
[http://dx.doi.org/10.1093/nar/gkv188] [PMID: 25769527]
[35]
Rascle, A.; Johnston, J.A.; Amati, B. Deacetylase activity is required for recruitment of the basal transcription machinery and transactivation by STAT5. Mol. Cell. Biol., 2003, 23(12), 4162-4173.
[http://dx.doi.org/10.1128/MCB.23.12.4162-4173.2003] [PMID: 12773560]
[36]
Rascle, A.; Lees, E. Chromatin acetylation and remodeling at the Cis promoter during STAT5-induced transcription. Nucleic Acids Res., 2003, 31(23), 6882-6890.
[http://dx.doi.org/10.1093/nar/gkg907] [PMID: 14627821]
[37]
Liu, S.; Walker, S.R.; Nelson, E.A.; Cerulli, R.; Xiang, M.; Toniolo, P.A.; Qi, J.; Stone, R.M.; Wadleigh, M.; Bradner, J.E.; Frank, D.A. Targeting STAT5 in hematologic malignancies through inhibition of the bromodomain and extra-terminal (BET) bromodomain protein BRD2. Mol. Cancer Ther., 2014, 13(5), 1194-1205.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0341] [PMID: 24435449]
[38]
Noguchi-Yachide, T.; Sakai, T.; Hashimoto, Y.; Yamaguchi, T. Discovery and structure-activity relationship studies of N6-benzoyladenine derivatives as novel BRD4 inhibitors. Bioorg. Med. Chem., 2015, 23(5), 953-959.
[http://dx.doi.org/10.1016/j.bmc.2015.01.022] [PMID: 25678016]
[39]
Falkenberg, K.J.; Johnstone, R.W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat. Rev. Drug Discov., 2014, 13(9), 673-691.
[http://dx.doi.org/10.1038/nrd4360] [PMID: 25131830]
[40]
Amemiya, S.; Yamaguchi, T.; Hashimoto, Y.; Noguchi-Yachide, T. Synthesis and evaluation of novel dual BRD4/HDAC inhibitors. Bioorg. Med. Chem., 2017, 25(14), 3677-3684.
[http://dx.doi.org/10.1016/j.bmc.2017.04.043] [PMID: 28549889]
[41]
Shao, M.; He, L.; Zheng, L.; Huang, L.; Zhou, Y.; Wang, T.; Chen, Y.; Shen, M.; Wang, F.; Yang, Z.; Chen, L. Structure-based design, synthesis and in vitro antiproliferative effects studies of novel dual BRD4/HDAC inhibitors. Bioorg. Med. Chem. Lett., 2017, 27(17), 4051-4055.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.054] [PMID: 28765013]
[42]
Cheng, G.; Wang, Z.; Yang, J.; Bao, Y.; Xu, Q.; Zhao, L.; Liu, D. Design, synthesis and biological evaluation of novel indole derivatives as potential HDAC/BRD4 dual inhibitors and anti-leukemia agents. Bioorg. Chem., 2019, 84, 410-417.
[http://dx.doi.org/10.1016/j.bioorg.2018.12.011] [PMID: 30554080]
[43]
Zhang, Z.; Hou, S.; Chen, H.; Ran, T.; Jiang, F.; Bian, Y.; Zhang, D.; Zhi, Y.; Wang, L.; Zhang, L.; Li, H.; Zhang, Y.; Tang, W.; Lu, T.; Chen, Y. Targeting epigenetic reader and eraser: rational design, synthesis and in vitro evaluation of dimethylisoxazoles derivatives as BRD4/HDAC dual inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(12), 2931-2935.
[http://dx.doi.org/10.1016/j.bmcl.2016.04.034] [PMID: 27142751]
[44]
Atkinson, S.J.; Soden, P.E.; Angell, D.C.; Bantscheff, M.; Chung, C.W.; Giblin, K.A.; Smithers, N.; Furze, R.C.; Gordon, L.; Drewes, G.; Rioja, I.; Witherington, J.; Parra, N.J.; Prinjhaa, R.K. The structure based design of dual HDAC/BET inhibitors as novel epigenetic probes. MedChemComm, 2014, 5(3), 342-351.
[http://dx.doi.org/10.1039/C3MD00285C]
[45]
Fruman, D.A.; Rommel, C. PI3K and cancer: lessons, challenges and opportunities. Nat. Rev. Drug Discov., 2014, 13(2), 140-156.
[http://dx.doi.org/10.1038/nrd4204] [PMID: 24481312]
[46]
Dey, N.; Leyland-Jones, B.; De, P. MYC-xing it up with PIK3CA mutation and resistance to PI3K inhibitors: summit of two giants in breast cancers. Am. J. Cancer Res., 2014, 5(1), 1-19.
[PMID: 25628917]
[47]
Knoepfler, P.S.; Kenney, A.M. Neural precursor cycling at sonic speed: N-Myc pedals, GSK-3 brakes. Cell Cycle, 2006, 5(1), 47-52.
[http://dx.doi.org/10.4161/cc.5.1.2292] [PMID: 16322694]
[48]
Nicodeme, E.; Jeffrey, K.L.; Schaefer, U.; Beinke, S.; Dewell, S.; Chung, C.W.; Chandwani, R.; Marazzi, I.; Wilson, P.; Coste, H.; White, J.; Kirilovsky, J.; Rice, C.M.; Lora, J.M.; Prinjha, R.K.; Lee, K.; Tarakhovsky, A. Suppression of inflammation by a synthetic histone mimic. Nature, 2010, 468(7327), 1119-1123.
[http://dx.doi.org/10.1038/nature09589] [PMID: 21068722]
[49]
Filippakopoulos, P.; Qi, J.; Picaud, S.; Shen, Y.; Smith, W.B.; Fedorov, O.; Morse, E.M.; Keates, T.; Hickman, T.T.; Felletar, I.; Philpott, M.; Munro, S.; McKeown, M.R.; Wang, Y.; Christie, A.L.; West, N.; Cameron, M.J.; Schwartz, B.; Heightman, T.D.; La Thangue, N.; French, C.A.; Wiest, O.; Kung, A.L.; Knapp, S.; Bradner, J.E. Selective inhibition of BET bromodomains. Nature, 2010, 468(7327), 1067-1073.
[http://dx.doi.org/10.1038/nature09504] [PMID: 20871596]
[50]
Zhang, G.; Smith, S.G.; Zhou, M.M. Discovery of chemical inhibitors of human bromodomains. Chem. Rev., 2015, 115(21), 11625-11668.
[http://dx.doi.org/10.1021/acs.chemrev.5b00205] [PMID: 26492937]
[51]
Delmore, J.E.; Issa, G.C.; Lemieux, M.E.; Rahl, P.B.; Shi, J.; Jacobs, H.M.; Kastritis, E.; Gilpatrick, T.; Paranal, R.M.; Qi, J.; Chesi, M.; Schinzel, A.C.; McKeown, M.R.; Heffernan, T.P.; Vakoc, C.R.; Bergsagel, P.L.; Ghobrial, I.M.; Richardson, P.G.; Young, R.A.; Hahn, W.C.; Anderson, K.C.; Kung, A.L.; Bradner, J.E.; Mitsiades, C.S. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell, 2011, 146(6), 904-917.
[http://dx.doi.org/10.1016/j.cell.2011.08.017] [PMID: 21889194]
[52]
Mertz, J.A.; Conery, A.R.; Bryant, B.M.; Sandy, P.; Balasubramanian, S.; Mele, D.A.; Bergeron, L.; Sims, R.J. III Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc. Natl. Acad. Sci. USA, 2011, 108(40), 16669-16674.
[http://dx.doi.org/10.1073/pnas.1108190108] [PMID: 21949397]
[53]
Crawford, N.P.; Alsarraj, J.; Lukes, L.; Walker, R.C.; Officewala, J.S.; Yang, H.H.; Lee, M.P.; Ozato, K.; Hunter, K.W. Bromodomain 4 activation predicts breast cancer survival. Proc. Natl. Acad. Sci. USA, 2008, 105(17), 6380-6385.
[http://dx.doi.org/10.1073/pnas.0710331105] [PMID: 18427120]
[54]
Shi, J.; Wang, Y.; Zeng, L.; Wu, Y.; Deng, J.; Zhang, Q.; Lin, Y.; Li, J.; Kang, T.; Tao, M.; Rusinova, E.; Zhang, G.; Wang, C.; Zhu, H.; Yao, J.; Zeng, Y.X.; Evers, B.M.; Zhou, M.M.; Zhou, B.P. Disrupting the interaction of BRD4 with diacetylated Twist suppresses tumorigenesis in basal-like breast cancer. Cancer Cell, 2014, 25(2), 210-225.
[http://dx.doi.org/10.1016/j.ccr.2014.01.028] [PMID: 24525235]
[55]
Dawson, M.A.; Prinjha, R.K.; Dittmann, A.; Giotopoulos, G.; Bantscheff, M.; Chan, W.I.; Robson, S.C.; Chung, C.W.; Hopf, C.; Savitski, M.M.; Huthmacher, C.; Gudgin, E.; Lugo, D.; Beinke, S.; Chapman, T.D.; Roberts, E.J.; Soden, P.E.; Auger, K.R.; Mirguet, O.; Doehner, K.; Delwel, R.; Burnett, A.K.; Jeffrey, P.; Drewes, G.; Lee, K.; Huntly, B.J.; Kouzarides, T. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature, 2011, 478(7370), 529-533.
[http://dx.doi.org/10.1038/nature10509] [PMID: 21964340]
[56]
Puissant, A.; Frumm, S.M.; Alexe, G.; Bassil, C.F.; Qi, J.; Chanthery, Y.H.; Nekritz, E.A.; Zeid, R.; Gustafson, W.C.; Greninger, P.; Garnett, M.J.; McDermott, U.; Benes, C.H.; Kung, A.L.; Weiss, W.A.; Bradner, J.E.; Stegmaier, K. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov., 2013, 3(3), 308-323.
[http://dx.doi.org/10.1158/2159-8290.CD-12-0418] [PMID: 23430699]
[57]
Bendell, J.C.; Rodon, J.; Burris, H.A.; de Jonge, M.; Verweij, J.; Birle, D.; Demanse, D.; De Buck, S.S.; Ru, Q.C.; Peters, M.; Goldbrunner, M.; Baselga, J. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J. Clin. Oncol., 2012, 30(3), 282-290.
[http://dx.doi.org/10.1200/JCO.2011.36.1360] [PMID: 22162589]
[58]
Janku, F.; Wheler, J.J.; Westin, S.N.; Moulder, S.L.; Naing, A.; Tsimberidou, A.M.; Fu, S.; Falchook, G.S.; Hong, D.S.; Garrido-Laguna, I.; Luthra, R.; Lee, J.J.; Lu, K.H.; Kurzrock, R. PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. J. Clin. Oncol., 2012, 30(8), 777-782.
[http://dx.doi.org/10.1200/JCO.2011.36.1196] [PMID: 22271473]
[59]
Zhu, H.; Mao, J.H.; Wang, Y.; Gu, D.H.; Pan, X.D.; Shan, Y.; Zheng, B. Dual inhibition of BRD4 and PI3K-AKT by SF2523 suppresses human renal cell carcinoma cell growth. Oncotarget, 2017, 8(58), 98471-98481.
[http://dx.doi.org/10.18632/oncotarget.21432] [PMID: 29228703]
[60]
Singh, A.R.; Joshi, S.; Burgoyne, A.M.; Sicklick, J.K.; Ikeda, S.; Kono, Y.; Garlich, J.R.; Morales, G.A.; Durden, D.L. Single agent and synergistic activity of the “first in class” dual PI3K/BRD4 inhibitor SF1126 with Sorafenib in hepatocellular carcinoma. Mol. Cancer Ther., 2016, 15(11), 2553-2562.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0976] [PMID: 27496136]
[61]
Stratikopoulos, E.E.; Dendy, M.; Szabolcs, M.; Khaykin, A.J.; Lefebvre, C.; Zhou, M.M.; Parsons, R. Kinase and BET inhibitors together clamp inhibition of PI3K signaling and overcome resistance to therapy. Cancer Cell, 2015, 27(6), 837-851.
[http://dx.doi.org/10.1016/j.ccell.2015.05.006] [PMID: 26058079]
[62]
Liu, X.; Wu, H.; Huang, P.; Zhang, F. JQ1 and PI3K inhibition synergistically reduce salivary adenoid cystic carcinoma malignancy by targeting the c-Myc and EGFR signaling pathways. J. Oral Pathol. Med., 2019, 48(1), 43-51.
[http://dx.doi.org/10.1111/jop.12784] [PMID: 30269363]
[63]
Morales, G.A.; Garlich, J.R.; Su, J.; Peng, X.; Newblom, J.; Weber, K.; Durden, D.L. Synthesis and cancer stem cell-based activity of substituted 5-morpholino-7H-thieno[3,2-b]pyran-7-ones designed as next generation PI3K inhibitors. J. Med. Chem., 2013, 56(5), 1922-1939.
[http://dx.doi.org/10.1021/jm301522m] [PMID: 23410005]
[64]
Andrews, F.H.; Singh, A.R.; Joshi, S.; Smith, C.A.; Morales, G.A.; Garlich, J.R.; Durden, D.L.; Kutateladze, T.G. 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.
[http://dx.doi.org/10.1073/pnas.1613091114] [PMID: 28137841]
[65]
Combes, G.; Alharbi, I.; Braga, L.G.; Elowe, S. Playing polo during mitosis: PLK1 takes the lead. Oncogene, 2017, 36(34), 4819-4827.
[http://dx.doi.org/10.1038/onc.2017.113] [PMID: 28436952]
[66]
Reid, R.J.D.; Du, X.; Sunjevaric, I.; Rayannavar, V.; Dittmar, J.; Bryant, E.; Maurer, M.; Rothstein, R. A synthetic dosage lethal genetic interaction between CKS1B and PLK1 is conserved in yeast and human cancer cells. Genetics, 2016, 204(2), 807-819.
[http://dx.doi.org/10.1534/genetics.116.190231] [PMID: 27558135]
[67]
de Cárcer, G.; Manning, G.; Malumbres, M. From Plk1 to Plk5: functional evolution of polo-like kinases. Cell Cycle, 2011, 10(14), 2255-2262.
[http://dx.doi.org/10.4161/cc.10.14.16494] [PMID: 21654194]
[68]
Lee, K.S.; Burke, T.R., Jr; Park, J.E.; Bang, J.K.; Lee, E. Recent advances and new strategies in targeting Plk1 for anticancer therapy. Trends Pharmacol. Sci., 2015, 36(12), 858-877.
[http://dx.doi.org/10.1016/j.tips.2015.08.013] [PMID: 26478211]
[69]
Li, Z.; Liu, J.; Li, J.; Kong, Y.; Sandusky, G.; Rao, X.; Liu, Y.; Wan, J.; Liu, X. Polo-like kinase 1 (Plk1) overexpression enhances ionizing radiation-induced cancer formation in mice. J. Biol. Chem., 2017, 292(42), 17461-17472.
[http://dx.doi.org/10.1074/jbc.M117.810960] [PMID: 28900036]
[70]
Strebhardt, K. Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat. Rev. Drug Discov., 2010, 9(8), 643-660.
[http://dx.doi.org/10.1038/nrd3184] [PMID: 20671765]
[71]
Cholewa, B.D.; Liu, X.; Ahmad, N. The role of polo-like kinase 1 in carcinogenesis: cause or consequence? Cancer Res., 2013, 73(23), 6848-6855.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-2197] [PMID: 24265276]
[72]
Shakil, S.; Baig, M.H.; Tabrez, S.; Rizvi, S.M.D.; Zaidi, S.K.; Ashraf, G.M.; Ansari, S.A.; Khan, A.A.P.; Al-Qahtani, M.H.; Abuzenadah, A.M.; Chaudhary, A.G. Molecular and enzoinformatics perspectives of targeting polo-like kinase 1 in cancer therapy. Semin. Cancer Biol., 2019, 56, 47-55.
[http://dx.doi.org/10.1016/j.semcancer.2017.11.004] [PMID: 29122685]
[73]
Liu, X.; Erikson, R.L. Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells. Proc. Natl. Acad. Sci. USA, 2003, 100(10), 5789-5794.
[http://dx.doi.org/10.1073/pnas.1031523100] [PMID: 12732729]
[74]
Liu, X.; Lei, M.; Erikson, R.L. Normal cells, but not cancer cells, survive severe Plk1 depletion. Mol. Cell. Biol., 2006, 26(6), 2093-2108.
[http://dx.doi.org/10.1128/MCB.26.6.2093-2108.2006] [PMID: 16507989]
[75]
Guan, R.; Tapang, P.; Leverson, J.D.; Albert, D.; Giranda, V.L.; Luo, Y. Small interfering RNA-mediated Polo-like kinase 1 depletion preferentially reduces the survival of p53-defective, oncogenic transformed cells and inhibits tumor growth in animals. Cancer Res., 2005, 65(7), 2698-2704.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-2131] [PMID: 15805268]
[76]
Tontsch-Grunt, U.; Rudolph, D.; Waizenegger, I.; Baum, A.; Gerlach, D.; Engelhardt, H.; Wurm, M.; Savarese, F.; Schweifer, N.; Kraut, N. Synergistic activity of BET inhibitor BI 894999 with PLK inhibitor volasertib in AML in vitro and in vivo. Cancer Lett., 2018, 421, 112-120.
[http://dx.doi.org/10.1016/j.canlet.2018.02.018] [PMID: 29454094]
[77]
Mao, F.; Li, J.; Luo, Q.; Wang, R.; Kong, Y.; Carlock, C.; Liu, Z.; Elzey, B.D.; Liu, X. Plk1 inhibition enhances the efficacy of BET epigenetic reader blockade in castration-resistant prostate cancer. Mol. Cancer Ther., 2018, 17(7), 1554-1565.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0945] [PMID: 29716963]
[78]
Han, Y.; Lindner, S.; Bei, Y.; Garcia, H.D.; Timme, N.; Althoff, K.; Odersky, A.; Schramm, A.; Lissat, A.; Künkele, A.; Deubzer, H.E.; Eggert, A.; Schulte, J.H.; Henssen, A.G. Synergistic activity of BET inhibitor MK-8628 and PLK inhibitor Volasertib in preclinical models of medulloblastoma. Cancer Lett., 2019, 445, 24-33.
[http://dx.doi.org/10.1016/j.canlet.2018.12.012] [PMID: 30611741]
[79]
Renner, A.G.; Dos Santos, C.; Recher, C.; Bailly, C.; Créancier, L.; Kruczynski, A.; Payrastre, B.; Manenti, S. Polo-like kinase 1 is overexpressed in acute myeloid leukemia and its inhibition preferentially targets the proliferation of leukemic cells. Blood, 2009, 114(3), 659-662.
[http://dx.doi.org/10.1182/blood-2008-12-195867] [PMID: 19458358]
[80]
Garcia-Gutierrez, P.; Mundi, M.; Garcia-Dominguez, M. Association of bromodomain BET proteins with chromatin requires dimerization through the conserved motif B. J. Cell Sci., 2012, 125(Pt 15), 3671-3680.
[http://dx.doi.org/10.1242/jcs.105841] [PMID: 22595521]
[81]
Steegmaier, M.; Hoffmann, M.; Baum, A.; Lénárt, P.; Petronczki, M.; Krssák, M.; Gürtler, U.; Garin-Chesa, P.; Lieb, S.; Quant, J.; Grauert, M.; Adolf, G.R.; Kraut, N.; Peters, J.M.; Rettig, W.J. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Curr. Biol., 2007, 17(4), 316-322.
[http://dx.doi.org/10.1016/j.cub.2006.12.037] [PMID: 17291758]
[82]
Chen, L.; Yap, J.L.; Yoshioka, M.; Lanning, M.E.; Fountain, R.N.; Raje, M.; Scheenstra, J.A.; Strovel, J.W.; Fletcher, S. BRD4 structure-activity relationships of dual PLK1 kinase/BRD4 bromodomain inhibitor BI-2536. ACS Med. Chem. Lett., 2015, 6(7), 764-769.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00084] [PMID: 26191363]
[83]
Liu, S.; Yosief, H.O.; Dai, L.; Huang, H.; Dhawan, G.; Zhang, X.; Muthengi, A.M.; Roberts, J.; Buckley, D.L.; Perry, J.A.; Wu, L.; Bradner, J.E.; Qi, J.; Zhang, W. Structure-guided design and development of potent and selective dual bromodomain 4 (BRD4)/polo-like kinase 1 (PLK1) inhibitors. J. Med. Chem., 2018, 61(17), 7785-7795.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00765] [PMID: 30125504]
[84]
Hu, J.; Wang, Y.; Li, Y.; Xu, L.; Cao, D.; Song, S.; Damaneh, M.S.; Wang, X.; Meng, T.; Chen, Y.L.; Shen, J.; Miao, Z.; Xiong, B. Discovery of a series of dihydroquinoxalin-2(1H)-ones as selective BET inhibitors from a dual PLK1-BRD4 inhibitor. Eur. J. Med. Chem., 2017, 137, 176-195.
[http://dx.doi.org/10.1016/j.ejmech.2017.05.049] [PMID: 28586718]
[85]
Hunt, T. Maturation promoting factor, cyclin and the control of M-phase. Curr. Opin. Cell Biol., 1989, 1(2), 268-274.
[http://dx.doi.org/10.1016/0955-0674(89)90099-9] [PMID: 2576632]
[86]
Fang, F.; Newport, J.W. Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes. Cell, 1991, 66(4), 731-742.
[http://dx.doi.org/10.1016/0092-8674(91)90117-H] [PMID: 1652371]
[87]
Norbury, C.; Nurse, P. Animal cell cycles and their control. Annu. Rev. Biochem., 1992, 61, 441-470.
[http://dx.doi.org/10.1146/annurev.bi.61.070192.002301] [PMID: 1497317]
[88]
Fu, J.; Yoon, H.G.; Qin, J.; Wong, J. Regulation of P-TEFb elongation complex activity by CDK9 acetylation. Mol. Cell. Biol., 2007, 27(13), 4641-4651.
[http://dx.doi.org/10.1128/MCB.00857-06] [PMID: 17452463]
[89]
Sims, R.J., III; Belotserkovskaya, R.; Reinberg, D. Elongation by RNA polymerase II: the short and long of it. Genes Dev., 2004, 18(20), 2437-2468.
[http://dx.doi.org/10.1101/gad.1235904] [PMID: 15489290]
[90]
Bentley, D.L.; Groudine, M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature, 1986, 321(6071), 702-706.
[http://dx.doi.org/10.1038/321702a0] [PMID: 3520340]
[91]
Lu, H.; Xue, Y.; Yu, G.K.; Arias, C.; Lin, J.; Fong, S.; Faure, M.; Weisburd, B.; Ji, X.; Mercier, A.; Sutton, J.; Luo, K.; Gao, Z.; Zhou, Q. Compensatory induction of MYC expression by sustained CDK9 inhibition via a BRD4-dependent mechanism. eLife, 2015.4e06535
[http://dx.doi.org/10.7554/eLife.06535] [PMID: 26083714]
[92]
Moreno, N.; Holsten, T.; Mertins, J.; Zhogbi, A.; Johann, P.; Kool, M.; Meisterernst, M.; Kerl, K. Combined BRD4 and CDK9 inhibition as a new therapeutic approach in malignant rhabdoid tumors. Oncotarget, 2017, 8(49), 84986-84995.
[http://dx.doi.org/10.18632/oncotarget.18583] [PMID: 29156698]
[93]
Bahr, B.L.; Maughan, K.S.; Soh, K.K.; Bearss, J.J.; Kim, W.; Peterson, P.; Whatcott, C.; Siddiqui-Jain, A.; Warner, S.L.; Bearss, D.J. Abstract 2698: Combination strategies to target super enhancer transcriptional activity by CDK9 and BRD4 inhibition in acute myeloid leukemia. Cancer Res., 2015, 75(15)(Suppl.), 2698.
[http://dx.doi.org/10.1158/1538-7445.AM2015-2698]
[94]
Baker, E.K.; Taylor, S.; Gupte, A.; Sharp, P.P.; Walia, M.; Walsh, N.C.; Zannettino, A.C.W.; Chalk, A.M.; Burns, C.J.; Walkley, C.R. BET inhibitors induce apoptosis through a MYC independent mechanism and synergise with CDK inhibitors to kill osteosarcoma cells. Sci. Rep., 2015, 5, 10120.
[http://dx.doi.org/10.1038/srep10120] [PMID: 25944566]
[95]
Damsky, W.; King, B.A. JAK inhibitors in dermatology: The promise of a new drug class. J. Am. Acad. Dermatol., 2017, 76(4), 736-744.
[http://dx.doi.org/10.1016/j.jaad.2016.12.005] [PMID: 28139263]
[96]
Schwartz, D.M.; Bonelli, M.; Gadina, M.; O’Shea, J.J. Type I/II cytokines, JAKs and new strategies for treating autoimmune diseases. Nat. Rev. Rheumatol., 2016, 12(1), 25-36.
[http://dx.doi.org/10.1038/nrrheum.2015.167] [PMID: 26633291]
[97]
O’Shea, J.J.; Schwartz, D.M.; Villarino, A.V.; Gadina, M.; McInnes, I.B.; Laurence, A. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu. Rev. Med., 2015, 66(1), 311-328.
[http://dx.doi.org/10.1146/annurev-med-051113-024537] [PMID: 25587654]
[98]
Jiang, Q.; Jamieson, C. BET’ing on Dual JAK/BET inhibition as a therapeutic strategy for myeloproliferative neoplasms. Cancer Cell, 2018, 33(1), 3-5.
[http://dx.doi.org/10.1016/j.ccell.2017.12.007] [PMID: 29316431]
[99]
Gunawan, S.; Muhammad, A.; Ember, S.W.J.; Zhu, J.Y.; Jacobsen, R.A.; Berndt, N.; Que, T.L.; Reuther, G.W.; Lawrence, H.R.; Schonbrunn, E. Abstract 3643: Targeting the acetyl-lysine binding site of BRD4 with dual nanomolar BET-JAK2 inhibitors: A new anticancer therapeutic strategy. Cancer Res., 2015, 75(15)(Suppl.), 3643.
[http://dx.doi.org/10.1158/1538-7445.AM2015-3643 ]
[100]
Pardanani, A.; Hood, J.; Lasho, T.; Levine, R.L.; Martin, M.B.; Noronha, G.; Finke, C.; Mak, C.C.; Mesa, R.; Zhu, H.; Soll, R.; Gilliland, D.G.; Tefferi, A. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia, 2007, 21(8), 1658-1668.
[http://dx.doi.org/10.1038/sj.leu.2404750] [PMID: 17541402]
[101]
Stuhlmiller, T.J.; Miller, S.M.; Zawistowski, J.S.; Nakamura, K.; Beltran, A.S.; Duncan, J.S.; Angus, S.P.; Collins, K.A.L.; Granger, D.A.; Reuther, R.A.; Graves, L.M.; Gomez, S.M.; Kuan, P.F.; Parker, J.S.; Chen, X.; Sciaky, N.; Carey, L.A.; Earp, H.S.; Jin, J.; Johnson, G.L. Inhibition of lapatinib-Induced kinome reprogramming in ERBB2-Positive breast cancer by targeting BET family bromodomains. Cell Rep., 2015, 11(3), 390-404.
[http://dx.doi.org/10.1016/j.celrep.2015.03.037] [PMID: 25865888]
[102]
Liu, S.; Li, S.; Hai, J.; Wang, X.; Chen, T.; Quinn, M.M.; Gao, P.; Zhang, Y.; Ji, H.; Cross, D.A.E.; Wong, K.K. Targeting HER2 aberrations in non-small cell lung cancer with osimertinib. Clin. Cancer Res., 2018, 24(11), 2594-2604.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-1875] [PMID: 29298799]
[103]
Xu, C.; Buczkowski, K.A.; Zhang, Y.; Asahina, H.; Beauchamp, E.M.; Terai, H.; Li, Y.Y.; Meyerson, M.; Wong, K-K.; Hammerman, P.S. NSCLC driven by DDR2 mutation is sensitive to dasatinib and JQ1 combination Therapy. Mol. Cancer Ther., 2015, 14(10), 2382-2389.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0077] [PMID: 26206333]
[104]
Singleton, K.R.; Crawford, L.; Tsui, E.; Manchester, H.E.; Maertens, O.; Liu, X.; Liberti, M.V.; Magpusao, A.N.; Stein, E.M.; Tingley, J.P.; Frederick, D.T.; Boland, G.M.; Flaherty, K.T.; McCall, S.J.; Krepler, C.; Sproesser, K.; Herlyn, M.; Adams, D.J.; Locasale, J.W.; Cichowski, K.; Mukherjee, S.; Wood, K.C. Melanoma therapeutic strategies that select against resistance by exploiting MYC-driven evolutionary convergence. Cell Rep., 2017, 21(10), 2796-2812.
[http://dx.doi.org/10.1016/j.celrep.2017.11.022] [PMID: 29212027]
[105]
Nakamura, Y.; Hattori, N.; Iida, N.; Yamashita, S.; Mori, A.; Kimura, K.; Yoshino, T.; Ushijima, T. Targeting of super-enhancers and mutant BRAF can suppress growth of BRAF-mutant colon cancer cells via repression of MAPK signaling pathway. Cancer Lett., 2017, 402, 100-109.
[http://dx.doi.org/10.1016/j.canlet.2017.05.017] [PMID: 28576751]
[106]
Paoluzzi, L.; Hanniford, D.; Sokolova, E.; Osman, I.; Darvishian, F.; Wang, J.; Bradner, J.E.; Hernando, E. BET and BRAF inhibitors act synergistically against BRAF-mutant melanoma. Cancer Med., 2016, 5(6), 1183-1193.
[http://dx.doi.org/10.1002/cam4.667] [PMID: 27169980]
[107]
Ma, Y.; Wang, L.; Neitzel, L.R.; Loganathan, S.N.; Tang, N.; Qin, L.; Crispi, E.E.; Guo, Y.; Knapp, S.; Beauchamp, R.D.; Lee, E.; Wang, J. The MAPK pathway regulates intrinsic resistance to BET inhibitors in colorectal cancer. Clin. Cancer Res., 2017, 23(8), 2027-2037.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0453] [PMID: 27678457]
[108]
Jing, Y.; Zhang, Z.; Ma, P.; An, S.; Shen, Y.; Zhu, L.; Zhuang, G. Concomitant BET and MAPK blockade for effective treatment of ovarian cancer. Oncotarget, 2016, 7(3), 2545-2554.
[http://dx.doi.org/10.18632/oncotarget.6309] [PMID: 26575423]
[109]
Wyce, A.; Matteo, J.J.; Foley, S.W.; Felitsky, D.J.; Rajapurkar, S.R.; Zhang, X-P.; Musso, M.C.; Korenchuk, S.; Karpinich, N.O.; Keenan, K.M.; Stern, M.; Mathew, L.K.; McHugh, C.F.; McCabe, M.T.; Tummino, P.J.; Kruger, R.G.; Carpenter, C.; Barbash, O. MEK inhibitors overcome resistance to BET inhibition across a number of solid and hematologic cancers. Oncogenesis, 2018, 7(4), 35.
[http://dx.doi.org/10.1038/s41389-018-0043-9] [PMID: 29674704]
[110]
Echevarría-Vargas, I.M.; Reyes-Uribe, P.I.; Guterres, A.N.; Yin, X.; Kossenkov, A.V.; Liu, Q.; Zhang, G.; Krepler, C.; Cheng, C.; Wei, Z.; Somasundaram, R.; Karakousis, G.; Xu, W.; Morrissette, J.J.; Lu, Y.; Mills, G.B.; Sullivan, R.J.; Benchun, M.; Frederick, D.T.; Boland, G.; Flaherty, K.T.; Weeraratna, A.T.; Herlyn, M.; Amaravadi, R.; Schuchter, L.M.; Burd, C.E.; Aplin, A.E.; Xu, X.; Villanueva, J. Co-targeting BET and MEK as salvage therapy for MAPK and checkpoint inhibitor-resistant melanoma. EMBO Mol. Med., 2018, 10(5), e8446.
[http://dx.doi.org/10.15252/emmm.201708446] [PMID: 29650805]
[111]
Wong, C.; Laddha, S.V.; Tang, L.; Vosburgh, E.; Levine, A.J.; Normant, E.; Sandy, P.; Harris, C.R.; Chan, C.S.; Xu, E.Y. The bromodomain and extra-terminal inhibitor CPI203 enhances the antiproliferative effects of rapamycin on human neuroendocrine tumors. Cell Death Dis., 2014, 5(10), e1450.
[http://dx.doi.org/10.1038/cddis.2014.396] [PMID: 25299775]
[112]
Lee, D.H.; Qi, J.; Bradner, J.E.; Said, J.W.; Doan, N.B.; Forscher, C.; Yang, H.; Koeffler, H.P. Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int. J. Cancer, 2015, 136(9), 2055-2064.
[http://dx.doi.org/10.1002/ijc.29269] [PMID: 25307878]
[113]
Boi, M.; Gaudio, E.; Bonetti, P.; Kwee, I.; Bernasconi, E.; Tarantelli, C.; Rinaldi, A.; Testoni, M.; Cascione, L.; Ponzoni, M.; Mensah, A.A.; Stathis, A.; Stussi, G.; Riveiro, M.E.; Herait, P.; Inghirami, G.; Cvitkovic, E.; Zucca, E.; Bertoni, F. The BET bromodomain inhibitor OTX015 affects pathogenetic pathways in preclinical B-cell tumor models and synergizes with targeted drugs. Clin. Cancer Res., 2015, 21(7), 1628-1638.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1561] [PMID: 25623213]
[114]
Gaudio, E.; Tarantelli, C.; Ponzoni, M.; Odore, E.; Rezai, K.; Bernasconi, E.; Cascione, L.; Rinaldi, A.; Stathis, A.; Riveiro, E.; Cvitkovic, E.; Zucca, E.; Bertoni, F. Bromodomain inhibitor OTX015 (MK-8628) combined with targeted agents shows strong in vivo antitumor activity in lymphoma. Oncotarget, 2016, 7(36), 58142-58147.
[http://dx.doi.org/10.18632/oncotarget.10983] [PMID: 27494885]
[115]
Vázquez, R.; Riveiro, M.E.; Astorgues-Xerri, L.; Odore, E.; Rezai, K.; Erba, E.; Panini, N.; Rinaldi, A.; Kwee, I.; Beltrame, L.; Bekradda, M.; Cvitkovic, E.; Bertoni, F.; Frapolli, R.; D’Incalci, M. The bromodomain inhibitor OTX015 (MK-8628) exerts anti-tumor activity in triple-negative breast cancer models as single agent and in combination with everolimus. Oncotarget, 2017, 8(5), 7598-7613.
[http://dx.doi.org/10.18632/oncotarget.13814] [PMID: 27935867]
[116]
Bauer, K.; Berger, D.; Zielinski, C.C.; Valent, P.; Grunt, T.W. Hitting two oncogenic machineries in cancer cells: cooperative effects of the multi-kinase inhibitor ponatinib and the BET bromodomain blockers JQ1 or dBET1 on human carcinoma cells. Oncotarget, 2018, 9(41), 26491-26506.
[http://dx.doi.org/10.18632/oncotarget.25474] [PMID: 29899872]
[117]
Felgenhauer, J.; Tomino, L.; Selich-Anderson, J.; Bopp, E.; Shah, N. Dual BRD4 and AURKA inhibition is synergistic against MYCN-amplified and nonamplified neuroblastoma. Neoplasia, 2018, 20(10), 965-974.
[http://dx.doi.org/10.1016/j.neo.2018.08.002] [PMID: 30153557]
[118]
Kubbutat, M.H.; Jones, S.N.; Vousden, K.H. Regulation of p53 stability by Mdm2. Nature, 1997, 387(6630), 299-303.
[http://dx.doi.org/10.1038/387299a0] [PMID: 9153396]
[119]
Stewart, H.J.S.; Horne, G.A.; Bastow, S.; Chevassut, T.J.T. BRD4 associates with p53 in DNMT3A-mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1. Cancer Med., 2013, 2(6), 826-835.
[http://dx.doi.org/10.1002/cam4.146] [PMID: 24403256]
[120]
Brooks, C.L.; Gu, W. New insights into p53 activation. Cell Res., 2010, 20(6), 614-621.
[http://dx.doi.org/10.1038/cr.2010.53] [PMID: 20404858]
[121]
Hines, J.; Lartigue, S.; Dong, H.; Qian, Y.; Crews, C.M. MDM2-recruiting PROTAC offers superior, synergistic anti-proliferative activity via simultaneous degradation of BRD4 and stabilization of p53. Cancer Res., 2019, 79(1), 251-262.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2918] [PMID: 30385614]
[122]
Ashkenazi, A.; Fairbrother, W.J.; Leverson, J.D.; Souers, A.J. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat. Rev. Drug Discov., 2017, 16(4), 273-284.
[http://dx.doi.org/10.1038/nrd.2016.253] [PMID: 28209992]
[123]
Faber, A.C.; Farago, A.F.; Costa, C.; Dastur, A.; Gomez-Caraballo, M.; Robbins, R.; Wagner, B.L.; Rideout, W.M., III; Jakubik, C.T.; Ham, J.; Edelman, E.J.; Ebi, H.; Yeo, A.T.; Hata, A.N.; Song, Y.; Patel, N.U.; March, R.J.; Tam, A.T.; Milano, R.J.; Boisvert, J.L.; Hicks, M.A.; Elmiligy, S.; Malstrom, S.E.; Rivera, M.N.; Harada, H.; Windle, B.E.; Ramaswamy, S.; Benes, C.H.; Jacks, T.; Engelman, J.A. Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer. Proc. Natl. Acad. Sci. USA, 2015, 112(11), E1288-E1296.
[http://dx.doi.org/10.1073/pnas.1411848112] [PMID: 25737542]
[124]
Rudin, C.M.; Hann, C.L.; Garon, E.B.; Ribeiro de Oliveira, M.; Bonomi, P.D.; Camidge, D.R.; Chu, Q.; Giaccone, G.; Khaira, D.; Ramalingam, S.S.; Ranson, M.R.; Dive, C.; McKeegan, E.M.; Chyla, B.J.; Dowell, B.L.; Chakravartty, A.; Nolan, C.E.; Rudersdorf, N.; Busman, T.A.; Mabry, M.H.; Krivoshik, A.P.; Humerickhouse, R.A.; Shapiro, G.I.; Gandhi, L. Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin. Cancer Res., 2012, 18(11), 3163-3169.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-3090] [PMID: 22496272]
[125]
Li, Y.; Choi, P.S.; Casey, S.C.; Dill, D.L.; Felsher, D.W. MYC through miR-17-92 suppresses specific target genes to maintain survival, autonomous proliferation and a neoplastic state. Cancer Cell, 2014, 26(2), 262-272.
[http://dx.doi.org/10.1016/j.ccr.2014.06.014] [PMID: 25117713]
[126]
Wang, H.; Hong, B.; Li, X.; Deng, K.; Li, H.; Yan Lui, V.W.; Lin, W. JQ1 synergizes with the Bcl-2 inhibitor ABT-263 against MYCN-amplified small cell lung cancer. Oncotarget, 2017, 8(49), 86312-86324.
[http://dx.doi.org/10.18632/oncotarget.21146] [PMID: 29156797]
[127]
Peirs, S.; Frismantas, V.; Matthijssens, F.; Van Loocke, W.; Pieters, T.; Vandamme, N.; Lintermans, B.; Dobay, M.P.; Berx, G.; Poppe, B.; Goossens, S.; Bornhauser, B.C.; Bourquin, J.P.; Van Vlierberghe, P. Targeting BET proteins improves the therapeutic efficacy of BCL-2 inhibition in T-cell acute lymphoblastic leukemia. Leukemia, 2017, 31(10), 2037-2047.
[http://dx.doi.org/10.1038/leu.2017.10] [PMID: 28074072]
[128]
Bui, M.H.; Lin, X.; Albert, D.H.; Li, L.; Lam, L.T.; Faivre, E.J.; Warder, S.E.; Huang, X.; Wilcox, D.; Donawho, C.K.; Sheppard, G.S.; Wang, L.; Fidanze, S.; Pratt, J.K.; Liu, D.; Hasvold, L.; Uziel, T.; Lu, X.; Kohlhapp, F.; Fang, G.; Elmore, S.W.; Rosenberg, S.H.; McDaniel, K.F.; Kati, W.M.; Shen, Y. Preclinical characterization of BET family bromodomain inhibitor ABBV-075 suggests combination therapeutic strategies. Cancer Res., 2017, 77(11), 2976-2989.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-1793] [PMID: 28416490]
[129]
Lam, L.T.; Lin, X.; Faivre, E.J.; Yang, Z.; Huang, X.; Wilcox, D.M.; Bellin, R.J.; Jin, S.; Tahir, S.K.; Mitten, M.; Magoc, T.; Bhathena, A.; Kati, W.M.; Albert, D.H.; Shen, Y.; Uziel, T. Vulnerability of small cell lung cancer to apoptosis induced by the combination of BET bromodomain proteins and BCL2 inhibitors. Mol. Cancer Ther., 2017, 16(8), 1511-1520.
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0459] [PMID: 28468776]
[130]
Ishida, C.T.; Bianchetti, E.; Shu, C.; Halatsch, M.E.; Westhoff, M.A.; Karpel-Massler, G.; Siegelin, M.D. BH3-mimetics and BET-inhibitors elicit enhanced lethality in malignant glioma. Oncotarget, 2017, 8(18), 29558-29573.
[http://dx.doi.org/10.18632/oncotarget.16365] [PMID: 28418907]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy