Schematic representation of the therapeutic strategies that can be applied to target ARF876L. Schematic representation of the therapeutic strategies that.

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Schematic representation of the therapeutic strategies that can be applied to target ARF876L. Schematic representation of the therapeutic strategies that can be applied to target ARF876L. Left, MDV3100 (brown circles) suppresses expression of E2F1 and canonical AR target genes upon binding to AR-WT (red ovals). Middle, ARF876L (green ovals) uses MDV3100 as an agonist and thus maintains expression of E2F1 and canonical AR target genes. Right, targeting CDK4/6 or AR with structurally distinct antiandrogens can hinder proliferation through suppression of E2F1 and canonical AR target genes, respectively. Length of gray arrow represents relative level of pathway activity. Red and blue circles represent CDK4/6 inhibitor and bicalutamide, respectively. EBS, E2F1-binding sites; ARE, androgen-responsive elements. Manav Korpal et al. Cancer Discovery 2013;3:1030-1043 ©2013 by American Association for Cancer Research