Two potential explanations for differences in cuSCC induction rates between BRAFi emerged: (1) differing degrees of peak and time-integrated pERK/tERK induction and (2) different “paradox indices.” This measure, the paradox index, is meant to be an in-vitro estimation of a therapeutic window, reflecting a concentration range within which efficacy against BRAF-mutant melanoma cells is maximized while paradoxical ERK activation is minimized. The gene discussed is BRAF; the disease is melanoma.