CYT997 (lexibulin) (a microtubule-targeting agent), when used to treat osteosarcoma, damages mitochondria to produce ROS and also induces ERS, which exacerbates oxidative stress through the PERK/ eIF2α/CHOP/ERO1 axis, while ROS produced by the mitochondrial pathway also exacerbates ERS, ERS and oxidative stress enhance each other to promote apoptosis [72] (Figure 2). Here, EIF2AK3 is linked to osteosarcoma.