Treatment with either of the two specific IRE1 endoribonuclease inhibitors exerts no effect on the kinase activity and autophoshorylation of IRE1 but only marked inhibition of XBP1 splicing and its downstream substrates, which strongly demonstrates that the IRE1-XBP1 axis is essential for MM cell survival and targeting this pathway may result in marked anti-tumor effects (120). This evidence concerns the gene ERN1 and neoplasm.