# The Role of Se-Containing Glutathione Peroxidases and Thioredoxin Reductases in Oncogenesis: Expression Paradoxes and Therapeutic Prospects

## TL;DR

This review explores how selenium-containing antioxidant enzymes can act as both cancer promoters and suppressors, depending on the context, and their potential as therapeutic targets.

## Contribution

The paper provides a comprehensive analysis of the paradoxical roles of GPXs and TXNRDs in cancer and their therapeutic implications.

## Key findings

- GPXs and TXNRDs exhibit dual roles as oncogenes or tumor suppressors depending on the cancer context.
- GPX4 plays a key role in regulating ferroptosis, a potential target for cancer therapy.
- TXNRD overexpression is linked to poor prognosis in aggressive cancers.

## Abstract

This review synthesizes current evidence on the dualistic and context-dependent roles of selenium-containing antioxidant enzymes—specifically, glutathione peroxidases (GPXs) and thioredoxin reductases (TXNRDs)—in the development and progression of human cancers. We analyze how these crucial components of cellular redox homeostasis can function as either potent oncogenes or tumor suppressors depending on the tissue of origin, cancer stage, genetic background, and tumor microenvironment. The paradoxical behavior of these enzymes is governed by a complex interplay of transcriptional regulation, epigenetic modifications, and signaling pathway interactions, ultimately influencing critical processes such as apoptosis, proliferation, invasion, and therapy resistance. Special emphasis is placed on the unique role of GPX4 in regulating ferroptosis, a promising target for novel anti-cancer strategies, and on the prognostic significance of TXNRD overexpression in aggressive malignancies. By integrating data across various cancer types, this review highlights these enzyme families as central molecular switches in carcinogenesis and discusses their potential as biomarkers and targets for rational, combination-based therapeutic interventions.