IRE1α-XBP1 signaling pathway, a potential therapeutic target in multiple myeloma

• ER stress and UPR play a significant role in plasma differentiation and MM.
• IRE1α-XBP1 signaling pathway is an important branch of UPR.
• XBP1s levels could predict the prognosis of MM.
• XBP1s levels could assess the effect of thalidomide and bortezomib therapy.
• Many targeted drugs develop anti-tumor effect by regulating IRE1α-XBP1 pathway.

Multiple myeloma (MM), which arises from the uncontrolled proliferation of malignant plasma cells, is the second most commonly diagnosed hematologic malignancy in the United States. Despite the development and application of novel drugs and autologous stem cell transplantation (ASCT), MM remains an incurable disease and patients become more prone to MM relapse and drug resistance. It is extremely urgent to find novel targeted therapy for MM. To date, the classic signaling pathways underlying MM have included the RAS/RAF/MEK/ERK pathway, the JAK-STAT3 pathway, the PI3K/Akt pathway and the NF-KB pathway. The IRE1α-XBP1 signaling pathway is currently emerging as an important pathway involved in the development of MM. Moreover, it is closely associated with the effect of MM treatment and its prognosis. All these findings indicate that the IRE1α-XBP1 pathway can be a potential treatment target. Herein, we investigate the relationship between the IRE1α-XBP1 pathway and MM and discuss the functions of IRE1α-XBP1-targeted drugs in the treatment of MM.