Indeed, IRE1α endonuclease inhibitors such as toyocamycin, STF-083010 4μ8C, MKC-3946, and B-I09, which prevent XBP1 splicing, have been successfully exploited in MM [41,42], and other cancers [43] and could be considered as a therapeutic strategy to diminish cancer cell ability to live in harsh microenvironment conditions, such as hypoxia and nutrient deprivation, leading to increased drug sensitivity and reduced angiogenesis. The gene discussed is ERN1; the disease is cancer.