Mechanisms Driving Resistance to Proteasome Inhibitors Bortezomib, Carfilzomib, and Ixazomib in Multiple Myeloma

Melissa K. Bennett, Stuart M. Pitson, Craig T. Wallington-Beddoe

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

The first clinically available proteasome inhibitor (PI) bortezomib was trialed in multiple myeloma (MM) approximately two decades ago and has since become a mainstay of myeloma therapy, significantly enhancing the overall survival of patients. However, bortezomib resistance continues to be a significant hurdle in the treatment of MM, despite the introduction of next-generation PIs such as carfilzomib and ixazomib. Unlike resistance to some other targeted therapies such as tyrosine kinase inhibitors, bortezomib resistance is highly complex and is able to arise through multiple mechanisms. This chapter discusses the current known mechanisms underlying bortezomib resistance, as well as resistance to the next-generation proteasome inhibitors carfilzomib and ixazomib.
Original languageEnglish
Title of host publicationResistance to Targeted Therapies in Multiple Myeloma
EditorsSilvia Ling, Steven Trieu
Place of PublicationCham, Switzerland
PublisherSpringer Nature
Chapter4
Pages39-59
Number of pages21
ISBN (Electronic)9783030734404
ISBN (Print)9783030734398
DOIs
Publication statusPublished - 24 Jul 2021

Publication series

NameResistance of Targeted Anti-Cancer Therapeutics
Volume22
ISSN (Print)2196-5501

Keywords

  • Multiple myeloma
  • Proteasome inhibitors
  • Bortezomib
  • Carfilzomib
  • Ixazomib
  • Proteasome inhibitor resistance
  • Autophagy
  • Unfolded protein response

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