RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
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..., 2010) and in a range of hematological malignancies (Dawson et al., 2011; Delmore et al., 2011; Mertz et al., 2011; Zuber et al., 2011)....
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...The belief and investment in epigenetic cancer therapies may now gain momentum and reach a new level of support following the recent preclinical success of inhibitors against BRD4, an acetyl-lysine chromatin-binding protein (Dawson et al., 2011; Delmore et al., 2011; Filippakopoulos et al., 2010; Mertz et al., 2011; Zuber et al., 2011)....
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..., 2011); and, importantly, MYC overexpression fails to rescue the apoptosis induced by BET inhibition (Zuber et al., 2011)....
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...…the expression of MYC was noted to be substantially decreased in a variety of malignant hematopoietic cell lines, including MLL-translocated acute myeloid leukemia (Dawson et al., 2011; Zuber et al., 2011), multiple myeloma (Delmore et al., 2011), and Burkitt’s lymphoma (Mertz et al., 2011)....
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...The BET inhibitors have recently been shown to have excellent efficacy in NUT-midline carcinoma (Filippakopoulos et al., 2010) and in a range of hematological malignancies (Dawson et al., 2011; Delmore et al., 2011; Mertz et al., 2011; Zuber et al., 2011)....
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...Inhibitors of BRD4 suppress the expression of super-enhancer-associated genes such as MYC (Delmore et al., 2011; Mertz et al., 2011; Zuber et al., 2011), and small-molecule BET inhibitors are known to interfere with c-MYC-dependent transcriptional responses (Venkataraman et al....
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...In ER+ breast cancer cells, BET inhibitors also overcame resistance to everolimus caused by c-Myc overexpression (Bihani et al., 2015) and exerted synergistic antitumor activity with PI3K inhibitors in mice with mammary tumors initiated by oncogenic PI3K-H1047R plusMYC transgene expression (Stratikopoulos et al., 2015)....
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...Finally, primary or acquired resistance can also arise by activation of heterologous pathways leading to common endpoints; for instance, MYC-dependent transcriptional activation or ERK activity (in pink, ‘‘4’’)....
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...Inhibitors of BRD4 suppress the expression of super-enhancer-associated genes such as MYC (Delmore et al., 2011; Mertz et al., 2011; Zuber et al., 2011), and small-molecule BET inhibitors are known to interfere with c-MYC-dependent transcriptional responses (Venkataraman et al., 2014)....
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...Amplification of MYC drives resistance to PI3K/mTOR pathway inhibitors in breast cancer cell lines (Figure 6), andMYC copy number and/or c-Myc expression is often elevated in breast cancer (Ilic et al., 2011; Liu et al., 2012) and lymphoid malignancies (Dang, 2012)....
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References
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"RNAi screen identifies Brd4 as a th..." refers methods in this paper
...Diagnoses were established according to criteria provided by the French-American-British (FAB) cooperative study grou...
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"RNAi screen identifies Brd4 as a th..." refers background in this paper
...The recent development of small-molecule BET bromodomain inhibitor...
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