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In further contrast, JQ1 activity in OS was mediated independently of MYC downregulation. We identified that JQ1 suppresses the transcription factor FOSL1 by displacement of BRD4 from its locus. Loss of FOSL1 phenocopied the antiproliferative effects of JQ1, identifying FOSL1 suppression as a potential novel therapeutic approach for OS.

As a monotherapy JQ1 demonstrated significant anti-tumour activity in vivo in an OS graft model. Further, combinatorial treatment approaches showed that JQ1 increased the sensitivity of OS cells to doxorubicin and induced potent synergistic activity when rationally combined with CDK inhibitors.

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Port Vale. Leyton Orient. Further, combinatorial treatment approaches showed that JQ1 increased the sensitivity of OS cells to doxorubicin and induced potent synergistic activity when rationally combined with CDK inhibitors.

The greater level of activity achieved with the combination of BETi with CDK inhibitors demonstrates the efficacy of this combination therapy.

Taken together, our studies show that BET inhibitors are a promising new therapeutic for OS. Abstract Osteosarcoma OS survival rates have plateaued in part due to a lack of new therapeutic options.

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