Figure 2.

Mechanisms of BET inhibitor activity, resistance and combinatorial application. (A) Carcinogenic changes mediated by upregulation of tumorigenic transcription factors, anti-apoptotic genes, oncogenes and cell cycle inducers following epigenetic enhancement by BET proteins. (B) BET inhibitors induce anti-tumor effect by enhancing apoptosis and reducing cell proliferation. (C) Cell adaptation mechanisms to overcome BET inhibition by upregulation of receptors for epidermal growth factor (EGF-R), vascular endothelial growth factor (VEGF-R) and other stress mediated factors such as HIF1α etc. (D) Combinatorial treatment with addition of drugs targeted at mTOR pathway and other oncogenic pathways along with BET inhibition to enhance anti-cancer impact.