Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma?
Abstract
:Simple Summary
Abstract
1. Introduction
2. ERS and Drug-Resistance of MM
2.1. UPR Signaling: Canonical 3 Arms in MM
2.2. Altered ERSR Activation in Drug-Resistant MM
3. MM Cell Survival and ERSR
3.1. ERS-Induced Apoptosis and MM Drug Resistance
3.2. ERS-Mediated Autophagy and Survival of Drug-Resistant MM Cells
3.3. Survival/Apoptosis Balance under ERS and Its Implication for MM
4. ERS-Triggered Ca2+ Leakage and Its Role in Modulating MM Cell Fate
5. Emerging Strategies to Overcome MM Drug Resistance by Targeting ERS
Agent Name | Drug Target | Research Status in MM | Reference | |
---|---|---|---|---|
Research Phase | Combination Drug | |||
IPI-504 | HSP90 | Preclinical phase | Single | [139] |
PU-H71 | HSP90 | Preclinical phase | Single | [140] |
SNX-2112 | HSP90 | Preclinical phase | Single | [141] |
17-AAG | HSP90 | Clinical trial phase I/II | BZ | [142] |
AUY922 | HSP90 | Clinical trial phase I/Ib | Dex + BZ | [143] |
KW-2478 | HSP90 | Clinical trial phase I/II | BZ | [144] |
MAL3-101 | HSP70 | Preclinical phase | BZ | [145] |
PAT-SM6 | Grp78 | Clinical trial phase I | Single | [146] |
Radamide analogs | Grp94 | Preclinical phase | Single | [149] |
MKC3946 | IRE1α | Preclinical phase | BZ | [150] |
Compound 18 | IRE1α | Preclinical phase | BZ or Len | [57] |
B-AP15 | DUBs (19S) | Preclinical phase | BZ | [151] |
Pyrithione | DUBs (19S, 20S) | Preclinical phase | Single | [152] |
P5091 | DUBs (USP7) | Preclinical phase | BZ | [153] |
TAK-243 | UAE | Preclinical phase | Single | [154] |
HCQ/CQ | Autophagy | Clinical trial phase I | BZ | [157] |
Venetoclax | BCL-2 | Clinical trial phase I/II | Dex | [158] |
Peptide vaccination | Anti-apoptotic proteins | Clinical trial phase I | BZ | [159] |
AMG 397 | MCL-1 | Clinical trial terminated | Dex | [161] |
ABBV-467 | MCL-1 | Clinical trial terminated | Single | [161] |
MIK-665 | MCL-1 | Clinical trial phase I | Single | [161] |
Nelfinavir | HIV protease | Clinical trial phase I | Single | [167] |
6. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Wang, G.; Fan, F.; Sun, C.; Hu, Y. Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma? Cancers 2022, 14, 5340. https://doi.org/10.3390/cancers14215340
Wang G, Fan F, Sun C, Hu Y. Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma? Cancers. 2022; 14(21):5340. https://doi.org/10.3390/cancers14215340
Chicago/Turabian StyleWang, Guangqi, Fengjuan Fan, Chunyan Sun, and Yu Hu. 2022. "Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma?" Cancers 14, no. 21: 5340. https://doi.org/10.3390/cancers14215340
APA StyleWang, G., Fan, F., Sun, C., & Hu, Y. (2022). Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma? Cancers, 14(21), 5340. https://doi.org/10.3390/cancers14215340