Epigenetic Alterations As Vital Aspects of Bortezomib Molecular Action

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Jan 11

PMID 38201512

Authors

Piotr Kulig

Karolina Luczkowska

Estera Bakinowska

Bartlomiej Baumert

Boguslaw Machalinski

Affiliations

Soon will be listed here.

Abstract

Bortezomib (BTZ) is widely implemented in the treatment of multiple myeloma (MM). Its main mechanism of action is very well established. BTZ selectively and reversibly inhibits the 26S proteasome. More precisely, it interacts with the chymotryptic site of the 20S proteasome and therefore inhibits the degradation of proteins. This results in the intracellular accumulation of misfolded or otherwise defective proteins leading to growth inhibition and apoptosis. As well as interfering with the ubiquitin-proteasome complex, BTZ elicits various epigenetic alterations which contribute to its cytotoxic effects as well as to the development of BTZ resistance. In this review, we summarized the epigenetic alterations elicited by BTZ. We focused on modifications contributing to the mechanism of action, those mediating drug-resistance development, and epigenetic changes promoting the occurrence of peripheral neuropathy. In addition, there are therapeutic strategies which are specifically designed to target epigenetic changes. Herein, we also reviewed epigenetic agents which might enhance BTZ-related cytotoxicity or restore the sensitivity to BTZ of resistant clones. Finally, we highlighted putative future perspectives regarding the role of targeting epigenetic changes in patients exposed to BTZ.

Citing Articles

Prognostic Value of PSMB5 and Correlations with LC3II and Reactive Oxygen Species Levels in the Bone Marrow Mononuclear Cells of Bortezomib-Resistant Multiple Myeloma Patients.

Plakoula E, Kalampounias G, Alexis S, Verigou E, Kourakli A, Zafeiropoulou K Curr Issues Mol Biol. 2025; 47(1).

PMID: 39852147 PMC: 11763810. DOI: 10.3390/cimb47010032.

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