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The potential roles of Nrf2/Keap1 signaling in anticancer drug interactions

Jingya Wang1, Jin Yang1, Mingnan Cao2

  • 1State Key Laboratory of Natural and Biomimetic Drugs; Department of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Sciences, Beijing, 100191, PR China.

Current Research in Pharmacology and Drug Discovery
|December 15, 2021
PubMed

Insights

Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) signaling impacts cancer. Modulators of this pathway, found in drugs and herbs, may cause interactions with cancer therapies.

Area of Science:

  • Biochemistry
  • Cellular Biology
  • Pharmacology

Background:

  • Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) signaling regulates cellular antioxidant and drug metabolism pathways.
  • Dysregulation of Nrf2/Keap1 signaling is implicated in various diseases, including cancer, multiple sclerosis, and chronic kidney disease.
  • Nrf2/Keap1 pathway modulators are present in pharmaceuticals, herbal remedies, and dietary components.

Purpose of the Study:

  • To review the fundamental biochemistry and physiology of Nrf2/Keap1 signaling.
  • To identify Nrf2/Keap1 signaling modulators encountered by cancer patients.
  • To highlight anticancer drugs affected by Nrf2/Keap1 signaling.

Main Methods:

  • Literature review of Nrf2/Keap1 signaling.
  • Analysis of drugs, herbs, and dietary ingredients modulating Nrf2/Keap1.
  • Identification of anticancer agents sensitive to Nrf2/Keap1 pathway modulation.

Main Results:

  • Nrf2 plays a dual role in cancer, potentially promoting progression and therapy resistance.
  • Activation of Nrf2/Keap1 signaling can lead to resistance to cancer treatments.
  • Numerous common drugs, herbs, and dietary supplements interact with the Nrf2/Keap1 pathway.

Conclusions:

  • Potential drug-drug and herb-drug interactions involving Nrf2/Keap1 modulators must be considered in cancer therapy.
  • Understanding these interactions is crucial for optimizing cancer treatment outcomes.
  • Further research is needed to fully elucidate the clinical implications of Nrf2/Keap1 modulation in cancer patients.
Keywords:
Anticancer drugsDrug-drug interactionsHerb-drug interactionsNrf2 modulatorsNrf2/Keap1 signaling

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