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Biomedicines
Volume 14
Issue 2
10.3390/biomedicines14020263
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha–Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer

by
Kamilla Khojayeva
1,
Aiym Zhussipbekkyzy
1,
Dilbara Balkybayeva
1,
Karakat Sabit
1,
Lucia Rossetti Lopes
2,
Kamila Sagatbekova
1,
Assem Zhakupova
1 and
Mohamad Aljofan
1,*
1
Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan
2
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, Brazil
*
Author to whom correspondence should be addressed.
Biomedicines 2026, 14(2), 263; https://doi.org/10.3390/biomedicines14020263
Submission received: 6 December 2025 / Revised: 20 January 2026 / Accepted: 21 January 2026 / Published: 23 January 2026
(This article belongs to the Section Cancer Biology and Oncology)
Versions Notes

Abstract

The endoplasmic reticulum (ER) is critical in aiding cells in ensuring that proteins are folded and processed correctly, particularly during stressful situations. ER oxidoreductin-1 alpha (ERO1α) is an enzyme that is responsible for the formation of disulfide bonds during protein folding, along with protein disulfide isomerase (PDI). This redox pathway is often highly upregulated in cancer cells, allowing tumors to survive harsh conditions such as hypoxia and nutrient deprivation. This review discusses the role of the ERO1α–PDI system in cancer development through the regulation of oxidative stress, redox homeostasis, and tumor plasticity. It further shows the therapeutic potential of interrupting the ERO1α–PDI axis, which could lead to protein misfolding; enhanced generation of reactive oxygen species (ROS); and, eventually, cancer cell death.
Keywords: endoplasmic reticulum stress; ERO1α; PDI endoplasmic reticulum stress; ERO1α; PDI

Share and Cite

MDPI and ACS Style

Khojayeva, K.; Zhussipbekkyzy, A.; Balkybayeva, D.; Sabit, K.; Lopes, L.R.; Sagatbekova, K.; Zhakupova, A.; Aljofan, M. Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha–Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer. Biomedicines 2026, 14, 263. https://doi.org/10.3390/biomedicines14020263

AMA Style

Khojayeva K, Zhussipbekkyzy A, Balkybayeva D, Sabit K, Lopes LR, Sagatbekova K, Zhakupova A, Aljofan M. Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha–Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer. Biomedicines. 2026; 14(2):263. https://doi.org/10.3390/biomedicines14020263

Chicago/Turabian Style

Khojayeva, Kamilla, Aiym Zhussipbekkyzy, Dilbara Balkybayeva, Karakat Sabit, Lucia Rossetti Lopes, Kamila Sagatbekova, Assem Zhakupova, and Mohamad Aljofan. 2026. "Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha–Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer" Biomedicines 14, no. 2: 263. https://doi.org/10.3390/biomedicines14020263

APA Style

Khojayeva, K., Zhussipbekkyzy, A., Balkybayeva, D., Sabit, K., Lopes, L. R., Sagatbekova, K., Zhakupova, A., & Aljofan, M. (2026). Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha–Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer. Biomedicines, 14(2), 263. https://doi.org/10.3390/biomedicines14020263

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