Nrf2 in cancers: A double-edged sword

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.