“…Cancer cells can co-opt the UPR to mitigate ER stress caused by altered protein-folding requirements, mutations, aneuploidy, and harsh tumor microenvironments 23–26 . Cell lines derived from several cancer malignancies, including multiple myeloma (MM) 27–32 , chronic lymphocytic leukemia 33 , breast cancer 34–37 , and colon cancer 38–41 , can exhibit a significant dependency on IRE1 for growth and survival. Studies to date have attributed this dependency to IRE1’s enzymatic activation of XBP1s 27–32,34,37,42,43 ; and/or RIDD 7,44,45 .…”