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Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer

Pelin Telkoparan-Akillilar1, Emiliano Panieri2, Dilek Cevik1

  • 1Department of Medical Biology, Faculty of Medicine, Yuksek Ihtisas University, 06520 Ankara, Turkey.

Molecules (Basel, Switzerland)
|April 3, 2021
PubMed

Insights

The Nuclear factor-erytherythroid 2-related factor 2 (NRF2) pathway is crucial for cellular defense but often dysregulated in cancer, promoting tumor survival. Understanding this pathway is key to developing novel cancer therapies targeting its activators and inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Defense Mechanisms

Background:

  • Cancer remains a leading cause of mortality worldwide, necessitating innovative therapeutic strategies.
  • The Nuclear factor-erythroid 2-related factor 2 (NRF2) and Kelch-like ECH-associated protein 1 (KEAP1) pathway governs cellular responses to stress.
  • Dysregulation of the NRF2/KEAP1 pathway is implicated in cancer progression, enhancing tumor cell survival and metastasis.

Purpose of the Study:

  • To review the mechanisms of the normal and deregulated NRF2 signaling pathway in cancer.
  • To explore the role of NRF2 signaling in cancer-related functions, including survival and metastasis.
  • To examine potential drug candidates that target the NRF2 pathway for cancer therapy.

Main Methods:

  • Literature review of scientific publications on NRF2/KEAP1 signaling.
  • Analysis of the role of NRF2 in various cancer types.
  • Exploration of activators and inhibitors of the NRF2 pathway as therapeutic agents.

Main Results:

  • The NRF2/KEAP1 pathway plays a dual role in cancer, acting as a tumor suppressor in early stages and a promoter in later stages.
  • Deregulation of NRF2 is observed in numerous cancers, contributing to chemoresistance and poor prognosis.
  • Numerous compounds targeting NRF2 activators and inhibitors have shown promise in preclinical cancer models.

Conclusions:

  • The NRF2/KEAP1 pathway represents a critical target for novel cancer therapies.
  • Further research into NRF2 pathway modulators could lead to effective treatments for various cancers.
  • Understanding the complex role of NRF2 in cancer is essential for developing targeted therapeutic strategies.
Keywords:
Keap1Nrf2canceroxidative stress

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