Translation of early generation EIF2AK3 inhibitors to the clinical setting has been difficult due to overt toxicity to pancreatic β-cells in humans, however next generation inhibitors with greater selectivity for EIF2AK3 are currently undergoing clinical trial development.187,188 While these inhibitors are not currently under investigation for cancer-associated bone disease, relevant clinical trials and potential bone-related effects are summarized in Table 1. Here, EIF2AK3 is linked to cancer.