Peroxiredoxin 1, pyroptosis, and the emerging frontier in colorectal cancer therapy

Sep 23, 2026

Uploaded by Rowan

Colorectal cancer (CRC) remains a major global health challenge, with high recurrence and mortality despite advances in surgery, chemotherapy, and immunotherapy. A mechanism is described in which peroxiredoxin 1 (Prdx1) suppresses CRC progression by inducing pyroptosis, a pro-inflammatory programmed cell death. Released extracellularly, Prdx1 functions as a damage-associated molecular pattern and activates the NOD-, LRR- and pyrin domain-containing protein 3 inflammasome pathway, triggering caspase-1/gasdermin D–mediated membrane pore formation, tumor lysis, and interleukin-1β/interleukin-18 release.

LanguageEnglish

CategoryHealthcare

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Pages7

Reading Time18 min

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Editorial

Peroxiredoxin 1, pyroptosis, and the emerging frontier in colorectal cancer therapy

Abstract

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Introduction

| W | J | G | World Journal of
Gastroenterology | | --- | --- | --- | --- | Submit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Gastroenterol 2026 January 7; 32(1): 114184 DOI: 10.3748/wjg.v32.i1.114184 ISSN 1007-9327 (print) ISSN 2219-2840 (online) EDITORIAL Peroxiredoxin 1, pyroptosis, and the emerging frontier in colorectal cancer therapy Dharmendra Kumar Maurya Specialty type: Gastroenterology and hepatology Provenance and peer review: Invited article; Externally peer reviewed. Peer-review model: Single blind Peer-review report’s classification Scientific Quality: Grade A, Grade A, Grade B Novelty: Grade B, Grade B, Grade B Creativity or Innovation: Grade B, Grade B, Grade B Scientific Significance: Grade A, Grade B, Grade B P-Reviewer: Yang C, MD, PhD, Associate Professor, China; Zhou JH, MD, Associate Chief Physician, China Received: September 15, 2025 Revised: October 22, 2025 Accepted: November 21, 2025 Published online: January 7, 2026 Processing time: 113 Days and 14.6 Hours Dharmendra Kumar Maurya, Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, Maharashtra, India Corresponding author: Dharmendra Kumar Maurya, PhD, Associate professor, Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, 3-82-S, A-Block, Modular Laboratory, Mumbai 400085, Maharashtra, [India.](India. dkmaurya@barc.gov.in)[ dkmaurya@barc.gov.in](India. dkmaurya@barc.gov.in) Abstract Colorectal cancer (CRC) remains a major global health challenge, with high recurrence and mortality despite advances in surgery, chemotherapy, and immunotherapy. The study by He et al identifies a novel mechanism by which peroxiredoxin 1 (Prdx1) inhibits CRC progression through induction of pyroptosis, a pro-inflammatory form of programmed cell death. Traditionally viewed as an intracellular antioxidant that protects tumors from oxidative stress, Prdx1 assu-mesa paradoxical immunogenic role when released extracellularly as a damageassociated molecular pattern. Using patient samples, recombinant protein assays, and murine xenograft models, the authors demonstrate that Prdx1 activates the NOD-, LRR- and pyrin domain-containing protein 3 inflammasome/caspase- 1/gasdermin D pathway, triggering membrane pore formation, tumor cell lysis, and release of interleukin-1β/interleukin-18 . This cascade not only halts tumor proliferation, invasion, and migration but may also enhance anti-tumor immune surveillance. The study’s strengths include rigorous mechanistic validation, clinical cohort data, inhibitor-based causal proof, and in vivo confirmation. However, questions remain regarding the upstream receptor for Prdx1, heterogeneity across CRC subtypes, and the balance between therapeutic benefit and inflammatory toxicity. By establishing Prdx1-induced pyroptosis as a driver of tumor suppression, this work advances a promising paradigm in CRC therapy, linking cell death to immune activation and pointing toward future biomarker-driven, pyroptosis-based interventions. Key Words: Colorectal cancer; Peroxiredoxin 1; Pyroptosis; Damage-associated molecular pattern; Immunogenic cell death ©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved. WJG [https://www.wjgnet.com](https://www.wjgnet.com) 1 January 7, 2026 Volume 32 Issue 1 Maurya DK. Prdx1 and pyroptosis in CRC therapy Core Tip: Peroxiredoxin 1, long regarded as an intracellular antioxidant that protect tumors from oxidative stress, assumes a paradoxical role in colorectal cancer therapy. He et al reveal that extracellular peroxiredoxin 1 acts as a damage-associated molecular pattern, activating the NOD-, LRR-and pyrin domain-containing protein 3 inflammasome/caspase-1/gasdermin D pathway to trigger pyroptosis. This lytic, pro-inflammatory death suppresses colorectal cancer proliferation, invasion, and migration while amplifying inter

FAQs

How does peroxiredoxin 1 (Prdx1) influence colorectal cancer progression?

Prdx1 inhibits CRC progression by inducing pyroptosis, a pro-inflammatory form of programmed cell death.

What role does extracellular Prdx1 play in the described mechanism?

When released extracellularly, Prdx1 acts as a damage-associated molecular pattern (DAMP) that triggers inflammatory signaling.

Which signaling pathway is activated to drive pyroptosis in this work?

The study reports activation of the NOD-, LRR- and pyrin domain-containing protein 3 inflammasome, leading to caspase-1 activation and gasdermin D–mediated membrane pore formation.

Sep 23, 2026

Uploaded by Rowan