Fig 2.

Pharmacodynamic biomarkers from nine evaluable paired pre- and during-treatment (day 15, 2 to 4 hours after dabrafenib [D] plus trametinib [T] dosing) tumor biopsies. (A) Representative images of phosphorylated ERK (P-ERK) immunohistochemistry staining in pre- (left) and during-treatment (right) biopsies. (B) H scores for P-ERK and (C) percent change in P-ERK H score in patients with BRAF V600–mutant colorectal cancer (CRC) treated with dabrafenib (150 mg twice daily) and trametinib (2 mg daily) as compared with patients with BRAF-mutant melanoma treated with dabrafenib only (70 to 200 mg twice daily; P < .001 by paired t test).¹⁸ (D) Phosphorylated AKT H scores before and during treatment. (E) Change in abundance of specific proteins or phosphoproteins in during-treatment biopsies relative to paired pretreatment biopsies was analyzed by reverse-phase protein array. Targets showing greatest average increase (yellow) or decrease (blue) after treatment are shown. Specific targets of interest are labeled, with mitogen-activated protein kinase pathway targets shown in green and mammalian target of rapamycin pathway targets shown in purple. PDGFRβ, platelet-derived growth factor receptor–β.