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Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Signaling

Background:

  • The Nrf2/Keap1 pathway regulates cellular defense against oxidative stress and exogenous chemicals.
  • It maintains redox homeostasis and exhibits anti-inflammatory and anticancer activities by controlling cytoprotective genes.
  • Recent findings highlight a dual role for Nrf2 in cancer, with aberrant activation linked to poor prognosis.

Purpose of the Study:

  • To review the contradictory roles of Nrf2 in cancer, encompassing both protective and oncogenic functions.
  • To summarize the mechanisms by which constitutive Nrf2 activation promotes cancer progression.
  • To explore Nrf2 inhibitors as a potential therapeutic strategy for cancer treatment.

Main Methods:

  • Literature review of studies investigating the Nrf2/Keap1 pathway in cancer.
  • Analysis of research on Nrf2's role in cancer cell proliferation, apoptosis, self-renewal, chemoresistance, and radioresistance.
  • Compilation of information on discovered Nrf2 inhibitors for cancer therapy.

Main Results:

  • Constitutive Nrf2 activation in cancer promotes proliferation, metabolic reprogramming, apoptosis evasion, and cancer stem cell self-renewal.
  • Nrf2 contributes to chemoresistance, radioresistance, and inflammation-induced carcinogenesis.
  • Several Nrf2 inhibitors have been identified, suggesting therapeutic potential.

Conclusions:

  • Nrf2 plays a complex, dual role in cancer, acting in both prevention and progression.
  • Targeting Nrf2 represents a promising therapeutic approach for developing novel anticancer treatments.
  • Further research into Nrf2's functions could uncover new strategies for cancer therapy.