CASP8 and cancer: To specifically address the potential for cross resistance and to identify potential combination partners to prevent emergence of MEDI3039-resistant cells lacking CASP8, BID, FADD, or TNFRSF10B, which we anticipate may emerge clinically, we screened the MSTO-211H, H2804, and NCI-H28 knockout models with a library of 60 compounds (including MEDI3039) targeting diverse cancer pathways, with cell viability assessed at day 6 (Fig. 1E; Supplementary Fig. S1D and S1E; Supplementary Table S8).