The endoplasmic reticulum and its signaling pathways – a novel target for multiple myeloma treatment
Authors:
A. Dostálová 1; M. Vlachová 1; J. Gregorová 1; L. Moráň 2,3; L. Pečinka 1; V. Gabrielová 2; P. Vaňhara 2,4; S. Ševčíková 1,5
Authors‘ workplace:
Babákova myelomová skupina, Ústav patologické fyziologie, LF MU Brno
1; Ústav histologie a embryologie, LF MU Brno
2; Výzkumné centrum aplikované molekulární onkologie (RECAMO), MOÚ Brno
3; Mezinárodní centrum klinického výzkumu, LF MU (ICRC) a FN u sv. Anny v Brně
4; Oddělení klinické hematologie, FN Brno
5
Published in:
Klin Onkol 2023; 37(6): 440-446
Category:
Review
doi:
https://doi.org/10.48095/ccko2023440
Overview
Background: The endoplasmic reticulum (ER), an organelle composed of a system of cisternae and tubules, is essential for many cellular processes, including protein synthesis and transport. When misfolded proteins accumulate in the ER lumen, ER stress is induced, and the subsequent response to the disruption of homeostasis is the activation of the unfolded protein response (UPR). The purpose of this process is to restore homeostasis by increasing the capacity of the ER and its ability to fold proteins. Activation of the homeostatic UPR occurs via one of three transmembrane proteins, inositol-requiring enzyme 1a (IRE1a), protein kinase R-like ER kinase (PERK) and activating transcription factor 6 (ATF6). Failure of the attempt to restore homeostasis, on the other hand, leads to the development of terminal UPR and apoptosis via hyperactivation of the same proteins. Activation of UPR has been described in many malignancies, including multiple myeloma (MM), which is characterized by malignant transformation of plasma cells and increased monoclonal immunoglobulin synthesis, where the role of the ER is of particular importance. Despite advances in the treatment of MM, the disease remains difficult to treat and targeting signaling pathways associated with the UPR could, for example, enhance the effect of proteasome inhibitors.
Purpose: This review intends to present the molecular response to ER stress under physiological circumstances and in the context of cancer, particularly with regard to potential therapeutic targets in MM.
Keywords:
Multiple myeloma – Endoplasmic reticulum – unfolded protein response
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Clinical Oncology
2023 Issue 6
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