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

## TL;DR

This review explores how disrupting a protein folding system in cancer cells could lead to their death by causing protein misfolding and increasing harmful oxygen species.

## Contribution

The paper highlights the ERO1α–PDI redox interface as a novel therapeutic target in cancer.

## Key findings

- The ERO1α–PDI system is overactive in cancer cells, helping them survive stressful conditions.
- Inhibiting this system increases reactive oxygen species and causes protein misfolding in cancer cells.
- Targeting ERO1α–PDI could lead to cancer cell death and is a promising therapeutic strategy.

## 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.