Figure 5. GDC-0941 resistant clones are sensitive to inhibitors of the MAPK pathway in the presence of GDC-0941.
(A) SW48 and SW48 H1047R parental and GDC-0941 resistant clones treated with a dose escalation of a MEK inhibitor (G-573) with and without a constant 1.5 uM dose of GDC-0941 and assayed for viability 96 hrs after dosing. (B) SW48 and SW48 H1047R parental and GDC-0941 resistant clones treated with a dose escalation of an ERK inhibitor (G-824) with and without a constant 1.5 uM dose of GDC-0941 and assayed for viability 96 hrs after dosing. (C) SW48 and SW48 H1047R GDC-0941 resistant clones dosed with DMSO, GDC-0941 (1.5 uM), G-573 (1.0 uM), G-824 (1.0 uM) or combinations of these inhibitors at these concentrations. Lysates were collected 24 hrs post treatment. Cell lysates were prepared and analyzed by immunoblotting.