In vitro and in vivo sensitivity of isogenic cell lines to selumetinib treatment. A, Cell viability as measured by MTS colorimetric assays of NIH3T3-KRASG12C and NIH3T3-KRASG12D cells after treatment with increasing doses of selumetinib for 3 days. B, Concentration of selumetinib that caused 50% growth inhibition (GI50) of NIH3T3-KRASG12C and NIH3T3-KRASG12D cells after treatment with increasing doses of selumetinib for 3 days. C, NIH3T3 cells transduced with either KRASG12C or KRASG12D were treated for 12 hours with selumetinib (10 nmol/L), lysed and blotted with the indicated antibodies. D, 106 NIH3T3-KRASG12C or NIH3T3-KRASG12D cells were injected into female SHO mice. Mice were treated with 25 mg/kg selumetinib when tumors reached approximately 250 mm3. Tumor volume was measured twice every week until the end of treatment. **, P < 0.01; ***, P < 0.001.