ERN1 and prostate cancer: Of note, these inhibitors are capable of blocking the downstream XBP1 splicing without affecting the upstream IRE1α or PERK or ATF6 pathway, making them superior candidates for clinical trials with good tolerability, which explains that long-term usage of MKC8866 is effective in breast and prostate cancers in preclinical models, without causing substantial toxicity to normal tissues (Zhao et al., 2018; Sheng et al., 2019).