Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition
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چکیده
منابع مشابه
Targeting MYCN-Driven Transcription By BET-Bromodomain Inhibition.
PURPOSE Targeting BET proteins was previously shown to have specific antitumoral efficacy against MYCN-amplified neuroblastoma. We here assess the therapeutic efficacy of the BET inhibitor, OTX015, in preclinical neuroblastoma models and extend the knowledge on the role of BRD4 in MYCN-driven neuroblastoma. EXPERIMENTAL DESIGN The efficacy of OTX015 was assessed in in vitro and in vivo models...
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Ewing sarcomas (ES) are highly malignant bone or soft tissue tumors. Genetically, ES are defined by balanced chromosomal EWS/ETS translocations, which give rise to chimeric proteins (EWS-ETS) that generate an oncogenic transcriptional program associated with altered epigenetic marks throughout the genome. By use of an inhibitor (JQ1) blocking BET bromodomain binding proteins (BRDs) we strikingl...
متن کاملTargeting MYCN in neuroblastoma by BET bromodomain inhibition.
Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revea...
متن کاملTargeting BET bromodomain proteins in solid tumors
There is increasing interest in inhibitors targeting BET (bromodomain and extra-terminal) proteins because of the association between this family of proteins and cancer progression. BET inhibitors were initially shown to have efficacy in hematologic malignancies; however, a number of studies have now shown that BET inhibitors can also block progression of non-hematologic malignancies. In this R...
متن کاملBET bromodomain inhibition of MYC-amplified medulloblastoma.
PURPOSE MYC-amplified medulloblastomas are highly lethal tumors. Bromodomain and extraterminal (BET) bromodomain inhibition has recently been shown to suppress MYC-associated transcriptional activity in other cancers. The compound JQ1 inhibits BET bromodomain-containing proteins, including BRD4. Here, we investigate BET bromodomain targeting for the treatment of MYC-amplified medulloblastoma. ...
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ژورنال
عنوان ژورنال: Nature Medicine
سال: 2014
ISSN: 1078-8956,1546-170X
DOI: 10.1038/nm.3613