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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Dual-target Inhibitors Based on BRD4: Novel Therapeutic Approaches for Cancer

Author(s): Sitao Zhang, Yanzhao Chen, Chengsen Tian, Yujing He, Zeru Tian, Yichao Wan and Tingting Liu*

Volume 28, Issue 9, 2021

Published on: 10 June, 2020

Page: [1775 - 1795] Pages: 21

DOI: 10.2174/0929867327666200610174453

Price: $65


Background: Currently, cancer continues being a dramatically increasing and serious threat to public health. Although many anti-tumor agents have been developed in recent years, the survival rate of patients is not satisfactory. The poor prognosis of cancer patients is closely related to the occurrence of drug resistance. Therefore, it is urgent to develop new strategies for cancer treatment. Multi-target therapies aim to have additive or synergistic effects and reduce the potential for the development of resistance by integrating different pharmacophores into a single drug molecule. Given the fact that majority of diseases are multifactorial in nature, multi-target therapies are being exploited with increasing intensity, which has brought improved outcomes in disease models and obtained several compounds that have entered clinical trials. Thus, it is potential to utilize this strategy for the treatment of BRD4 related cancers. This review focuses on the recent research advances of dual-target inhibitors based on BRD4 in the aspect of anti-tumor.

Methods: We have searched the recent literatures about BRD4 inhibitors from the online resources and databases, such as pubmed, elsevier and google scholar.

Results: In the recent years, many efforts have been taken to develop dual-target inhibitors based on BRD4 as anti-cancer agents, such as HDAC/BRD4 dual inhibitors, PLK1/BRD4 dual inhibitors and PI3K/BRD4 dual inhibitors and so on. Most compounds display good anti-tumor activities.

Conclusion: Developing new anti-cancer agents with new scaffolds and high efficiency is a big challenge for researchers. Dual-target inhibitors based on BRD4 are a class of important bioactive compounds. Making structural modifications on the active dual-target inhibitors according to the corresponding structure-activity relationships is of benefit to obtain more potent anti-cancer leads or clinical drugs. This review will be useful for further development of new dual-target inhibitors based on BRD4 as anti-cancer agents.

Keywords: BRD4, anti-cancer, combined, drug design, dual-target, enzymatic/non-enzymatic protein.

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.
[] [PMID: 24606519]
Florence, B.; Faller, D.V. You bet-cha: a novel family of transcriptional regulators. Front. Biosci., 2001, 6(1), D1008-D1018.
[] [PMID: 11487468]
Donati, B.; Lorenzini, E.; Ciarrocchi, A. BRD4 and cancer: going beyond transcriptional regulation. Mol. Cancer, 2018, 17(1), 164-177.
[] [PMID: 30466442]
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.
[] [PMID: 10365964]
Wu, S.Y.; Chiang, C.M. The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J. Biol. Chem., 2007, 282(18), 13141-13145.
[] [PMID: 17329240]
Zeng, L.; Zhou, M-M. Bromodomain: an acetyl-lysine binding domain. FEBS Lett., 2002, 513(1), 124-128.
[] [PMID: 11911891]
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.
[] [PMID: 10938129]
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.
[] [PMID: 12840145]
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.
[] [PMID: 22464331]
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.
[] [PMID: 19794495]
Shi, J.; Vakoc, C.R. The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol. Cell, 2014, 54(5), 728-736.
[] [PMID: 24905006]
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.
[] [PMID: 16928766]
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.
[] [PMID: 21555454]
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.
[] [PMID: 26626481]
Chiang, C.M. Phospho-BRD4: transcription plasticity and drug targeting. Drug Discov. Today. Technol., 2016, 19, 17-22.
[] [PMID: 27769352]
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.
[] [PMID: 23317504]
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.
[] [PMID: 26301327]
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.
[] [PMID: 26735014]
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.
[] [PMID: 24260471]
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.
[] [PMID: 18223296]
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.
[] [PMID: 21814200]
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.
[] [PMID: 24568369]
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.
[] [PMID: 12429021]
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.
[] [PMID: 19065135]
Filippakopoulos, P.; Knapp, S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov., 2014, 13(5), 337-356.
[] [PMID: 24751816]
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.
[] [PMID: 24979794]
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.
[] [PMID: 29074567]
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.
[] [PMID: 26733615]
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.
[] [PMID: 24435446]
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.
[] [PMID: 26390243]
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.
[] [PMID: 29312470]
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.
[] [PMID: 26087189]
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.
[] [PMID: 29764852]
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.
[] [PMID: 25769527]
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.
[] [PMID: 12773560]
Rascle, A.; Lees, E. Chromatin acetylation and remodeling at the Cis promoter during STAT5-induced transcription. Nucleic Acids Res., 2003, 31(23), 6882-6890.
[] [PMID: 14627821]
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.
[] [PMID: 24435449]
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.
[] [PMID: 25678016]
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.
[] [PMID: 25131830]
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.
[] [PMID: 28549889]
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.
[] [PMID: 28765013]
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.
[] [PMID: 30554080]
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.
[] [PMID: 27142751]
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.
Fruman, D.A.; Rommel, C. PI3K and cancer: lessons, challenges and opportunities. Nat. Rev. Drug Discov., 2014, 13(2), 140-156.
[] [PMID: 24481312]
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]
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.
[] [PMID: 16322694]
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.
[] [PMID: 21068722]
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.
[] [PMID: 20871596]
Zhang, G.; Smith, S.G.; Zhou, M.M. Discovery of chemical inhibitors of human bromodomains. Chem. Rev., 2015, 115(21), 11625-11668.
[] [PMID: 26492937]
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.
[] [PMID: 21889194]
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.
[] [PMID: 21949397]
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.
[] [PMID: 18427120]
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.
[] [PMID: 24525235]
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.
[] [PMID: 21964340]
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.
[] [PMID: 23430699]
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.
[] [PMID: 22162589]
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.
[] [PMID: 22271473]
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.
[] [PMID: 29228703]
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.
[] [PMID: 27496136]
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.
[] [PMID: 26058079]
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.
[] [PMID: 30269363]
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.
[] [PMID: 23410005]
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.
[] [PMID: 28137841]
Combes, G.; Alharbi, I.; Braga, L.G.; Elowe, S. Playing polo during mitosis: PLK1 takes the lead. Oncogene, 2017, 36(34), 4819-4827.
[] [PMID: 28436952]
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.
[] [PMID: 27558135]
de Cárcer, G.; Manning, G.; Malumbres, M. From Plk1 to Plk5: functional evolution of polo-like kinases. Cell Cycle, 2011, 10(14), 2255-2262.
[] [PMID: 21654194]
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.
[] [PMID: 26478211]
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.
[] [PMID: 28900036]
Strebhardt, K. Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat. Rev. Drug Discov., 2010, 9(8), 643-660.
[] [PMID: 20671765]
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.
[] [PMID: 24265276]
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.
[] [PMID: 29122685]
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.
[] [PMID: 12732729]
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.
[] [PMID: 16507989]
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.
[] [PMID: 15805268]
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.
[] [PMID: 29454094]
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.
[] [PMID: 29716963]
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.
[] [PMID: 30611741]
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.
[] [PMID: 19458358]
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.
[] [PMID: 22595521]
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.
[] [PMID: 17291758]
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.
[] [PMID: 26191363]
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.
[] [PMID: 30125504]
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.
[] [PMID: 28586718]
Hunt, T. Maturation promoting factor, cyclin and the control of M-phase. Curr. Opin. Cell Biol., 1989, 1(2), 268-274.
[] [PMID: 2576632]
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.
[] [PMID: 1652371]
Norbury, C.; Nurse, P. Animal cell cycles and their control. Annu. Rev. Biochem., 1992, 61, 441-470.
[] [PMID: 1497317]
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.
[] [PMID: 17452463]
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.
[] [PMID: 15489290]
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.
[] [PMID: 3520340]
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
[] [PMID: 26083714]
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.
[] [PMID: 29156698]
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.
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.
[] [PMID: 25944566]
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.
[] [PMID: 28139263]
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.
[] [PMID: 26633291]
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.
[] [PMID: 25587654]
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.
[] [PMID: 29316431]
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.
[ ]
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.
[] [PMID: 17541402]
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.
[] [PMID: 25865888]
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.
[] [PMID: 29298799]
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.
[] [PMID: 26206333]
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.
[] [PMID: 29212027]
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.
[] [PMID: 28576751]
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.
[] [PMID: 27169980]
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.
[] [PMID: 27678457]
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.
[] [PMID: 26575423]
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.
[] [PMID: 29674704]
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.
[] [PMID: 29650805]
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.
[] [PMID: 25299775]
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.
[] [PMID: 25307878]
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.
[] [PMID: 25623213]
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.
[] [PMID: 27494885]
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.
[] [PMID: 27935867]
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.
[] [PMID: 29899872]
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.
[] [PMID: 30153557]
Kubbutat, M.H.; Jones, S.N.; Vousden, K.H. Regulation of p53 stability by Mdm2. Nature, 1997, 387(6630), 299-303.
[] [PMID: 9153396]
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.
[] [PMID: 24403256]
Brooks, C.L.; Gu, W. New insights into p53 activation. Cell Res., 2010, 20(6), 614-621.
[] [PMID: 20404858]
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.
[] [PMID: 30385614]
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.
[] [PMID: 28209992]
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.
[] [PMID: 25737542]
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.
[] [PMID: 22496272]
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.
[] [PMID: 25117713]
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.
[] [PMID: 29156797]
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.
[] [PMID: 28074072]
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.
[] [PMID: 28416490]
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.
[] [PMID: 28468776]
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.
[] [PMID: 28418907]

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