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NRF2: KEAPing Tumors Protected

Ray Pillai1,2,3, Makiko Hayashi1, Anastasia-Maria Zavitsanou1

  • 1Department of Pathology, Perlmutter Cancer Center, New York University School of Medicine, New York, New York.

Cancer Discovery
|February 1, 2022
PubMed

Insights

The Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway, normally protective, drives cancer growth and treatment resistance when activated. Understanding its dysregulation is key to developing new cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The KEAP1/NRF2 pathway is crucial for cellular defense against toxins and oxidative stress.
  • Aberrant activation of this pathway in cancer confers a survival advantage to tumor cells.
  • NRF2 activation promotes tumor initiation, progression, and resistance to therapy.

Purpose of the Study:

  • To review the role of KEAP1/NRF2 pathway dysregulation in cancer.
  • To elucidate mechanisms by which NRF2 activation promotes tumorigenesis.
  • To discuss therapeutic strategies targeting the NRF2 pathway in cancer.

Main Methods:

  • Literature review of genetic, epigenetic, and posttranslational alterations activating the KEAP1/NRF2 pathway.
  • Analysis of NRF2's role in cancer metabolism, stress response, and immune evasion.
  • Examination of clinical data on NRF2 pathway alterations and treatment resistance.

Main Results:

  • KEAP1/NRF2 pathway alterations are prevalent in various solid tumors.
  • Activated NRF2 rewires tumor metabolism, enhances proliferation, and suppresses stress.
  • NRF2 pathway activation is linked to resistance against diverse cancer therapies.

Conclusions:

  • Dysregulation of the KEAP1/NRF2 pathway is a significant driver of cancer hallmarks.
  • Targeting the NRF2 pathway presents a promising therapeutic avenue for overcoming treatment resistance.

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