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Updated: Jul 22, 2025

In Vivo Imaging of Reactive Oxygen Species in a Murine Wound Model
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The mechanistic insights of the antioxidant Keap1-Nrf2 pathway in oncogenesis: a deadly scenario

Anirban Goutam Mukherjee1, Abilash Valsala Gopalakrishnan2

  • 1Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India.

Medical Oncology (Northwood, London, England)
|July 22, 2023
PubMed

Insights

The Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is crucial for cell protection but can be hijacked in cancer. Aberrant Nrf2 activity promotes tumor growth and resistance, highlighting its role in cancer progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Stress Response

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is vital for cellular defense against oxidative, metabolic, and xenobiotic stress.
  • The Keap1-Nrf2 pathway regulates Nrf2 activity, playing a critical role in maintaining tissue integrity.
  • Dysregulation of the Keap1-Nrf2 pathway is implicated in various diseases, including cancer, making it a significant pharmacological target.

Purpose of the Study:

  • To explore the intricate relationship between the Keap1-Nrf2 pathway and cancer progression.
  • To emphasize the role of genetic mutations, metabolic reprogramming, and immune evasion driven by Nrf2 in tumorigenesis.
  • To discuss potential therapeutic strategies targeting the Keap1-Nrf2 pathway for cancer treatment.

Main Methods:

  • Review of existing literature on Keap1-Nrf2 pathway mutations in different cancer types.
  • Analysis of the impact of Nrf2 activation on cancer cell characteristics, including chemoresistance and apoptosis evasion.
  • Investigation of genetic and epigenetic modifications affecting Nrf2 regulation in neoplastic cells.

Main Results:

  • Keap1-Nrf2 pathway mutations are not universal but interact with specific driver mutations and tissue origins.
  • Augmented Nrf2 activity confers traits like resistance to therapy, invasiveness, and angiogenesis in cancer cells.
  • Altered Nrf2 activity stems from diverse genetic and epigenetic modifications impacting its regulation.

Conclusions:

  • The Keap1-Nrf2 pathway represents a critical adaptation mechanism in cancer, leveraging cytoprotective pathways for tumor growth.
  • Understanding Nrf2 pathway anomalies is key to developing targeted therapies for various cancers.
  • Modulating the Keap1-Nrf2 pathway offers promising therapeutic avenues for cancer treatment.
Keywords:
CancerCytoprotectionKeap 1Nrf2OncogeneROS

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