# Redox regulation meets metabolism: targeting PRDX2 to prevent hepatocellular carcinoma

## TL;DR

PRDX2 is a key protein linking liver metabolism issues to cancer, and targeting it could prevent liver cancer while protecting normal liver function.

## Contribution

PRDX2 is identified as a novel redox regulator connecting MASH to HCC, with potential as a chemoprevention target.

## Key findings

- PRDX2 inhibition restores metabolic balance and reduces tumor initiation in liver cancer models.
- PRDX2 promotes oncogenic signaling and stemness during liver cancer development.
- Targeting PRDX2 in hepatocytes blocks HCC progression without harming normal liver function.

## Abstract

Metabolic dysfunction‐associated steatohepatitis (MASH) is emerging as a major driver of hepatocellular carcinoma (HCC). Crouchet et al. identify PRDX2 as a key regulator linking oxidative stress, metabolic imbalance, and oncogenic signaling. Across multiple in vivo and in vitro models, PRDX2 inhibition restores metabolic homeostasis, reduces tumor initiation, and selectively impairs HCC cell survival. These findings highlight PRDX2 as a promising biomarker and hepatocyte‐directed target for chemoprevention, emphasizing the importance of the interplay between metabolism and liver cancer development.

PRDX2 acts as a central redox hub linking metabolic dysfunction‐associated steatohepatitis (MASH) to hepatocellular carcinoma (HCC). In normal hepatocytes, PRDX2 maintains redox balance and metabolic homeostasis under oxidative stress. In contrast, during malignant transformation, PRDX2 promotes oncogenic signaling, stemness, and tumor initiation. Hepatocyte‐specific PRDX2 inhibition blocks HCC progression while preserving normal liver function, identifying PRDX2 as a potential therapeutic target.