For example, using a physiologically-based pharmacokinetic model, Cilliers et al. predicted that, in high HER2 expressing tumors, current clinical doses of T-DM1 result in poor tumor penetration and predicted that the co-administration of unconjugated (i.e., “naked”) mAb with T-DM1 would increase the fraction of tumor cells that are exposed to lethal T-DM1 concentrations (Cilliers et al., 2016; Khera et al., 2018). This evidence concerns the gene ERBB2 and neoplasm.