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

Leuk Res. 2016 Oct;49:7-12. doi: 10.1016/j.leukres.2016.07.006. Epub 2016 Jul 22.

Abstract

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.

Keywords: IRE1α Multiple myeloma; Prognosis; Therapy; UPR; XBP1s.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endoribonucleases / drug effects
  • Humans
  • Molecular Targeted Therapy / methods*
  • Multiple Myeloma / drug therapy*
  • Protein-Serine-Threonine Kinases / drug effects
  • Signal Transduction / drug effects
  • X-Box Binding Protein 1 / drug effects

Substances

  • X-Box Binding Protein 1
  • XBP1 protein, human
  • ERN1 protein, human
  • Protein-Serine-Threonine Kinases
  • Endoribonucleases