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. Author manuscript; available in PMC: 2010 Nov 1.
Published in final edited form as: Cancer Res. 2009 Oct 20;69(21):8217–8222. doi: 10.1158/0008-5472.CAN-09-2223

Figure 1. Targeting coactivators for therapy.

Figure 1

Left panel: Coactivator (e.g., SRC-3/AIB1) regulates the coordinate expression of multiple downstream genes (ER-responsive; E2F1-responsive; Her-2 responsive; NF-κB responsive; and protein kinase [P13K/AKT] responsive). These TF-responsive genes are all required for proliferation and metastasis of cancer cells. Targeting the individual pathways by using SERMS/aromatase inhibitors (for ER) or Herceptin (for Her-2/neu) only inhibits one or two pathways (for combinations). Cancer growth is then slowed, but the other pathways are upregulated to compensate, thereby producing eventual resistance to the therapy.

Right panel: If the coactivator is targeted and its function inhibited, simultaneous suppression of all pathways occurs. This scenario blocks alternate pathway compensatory upregulation, decreasing the onset of eventual drug resistance.