Proteasome Inhibitors in Multiple Myeloma: Biological Insights on Mechanisms of Action or Resistance Informed by Functional Genomics

Constantine S Mitsiades

doi:10.1016/j.hoc.2023.12.016

Proteasome Inhibitors in Multiple Myeloma: Biological Insights on Mechanisms of Action or Resistance Informed by Functional Genomics

Hematol Oncol Clin North Am. 2024 Apr;38(2):321-336. doi: 10.1016/j.hoc.2023.12.016. Epub 2024 Jan 25.

Author

Constantine S Mitsiades¹

Affiliation

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Ludwig Center at Harvard, Boston, MA, USA. Electronic address: constantine_mitsiades@dfci.harvard.edu.

PMID: 38278626
DOI: 10.1016/j.hoc.2023.12.016

Abstract

During the last 20 years, proteasome inhibitors have been a cornerstone for the therapeutic management of multiple myeloma (MM). This review highlights how MM research has evolved over time in terms of our understanding of the mechanistic basis for the pronounced clinical activity of proteasome inhibitors in MM, compared with the limited clinical applications of this drug class outside the setting of plasma cell dyscrasias.

Keywords: CRISPR; Endoplasmic reticulum-associated degradation; Functional genomics; Multiple myeloma; Nuclear Factor-kappa B (NF-κB); Proteasome inhibitors.

Publication types

Review

MeSH terms

Bortezomib / therapeutic use
Genomics
Humans
Multiple Myeloma* / drug therapy
Multiple Myeloma* / genetics
NF-kappa B / therapeutic use
Proteasome Inhibitors* / pharmacology
Proteasome Inhibitors* / therapeutic use

Substances

Proteasome Inhibitors
NF-kappa B
Bortezomib