Small molecular Nrf2 inhibitors as chemosensitizers for cancer therapy

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Nuclear factor erythroid 2-related factor 2 (Nrf2) is the main regulator of cellular oxidative stress.
• Nrf2 activation is a potential therapeutic strategy for various diseases.
• Aberrant Nrf2 hyperactivation is implicated in cancer progression, metastasis, and therapeutic resistance.

Purpose of the Study:

• To summarize the biological and pathological roles of Nrf2 in cancer.
• To review recent advancements in small molecular Nrf2 inhibitors.
• To explore potential Nrf2 inhibitory mechanisms for cancer treatment.

Main Methods:

• Literature review of Nrf2's function in cancer.
• Analysis of recent studies on small molecule Nrf2 inhibitors.
• Synthesis of information on Nrf2 inhibitory mechanisms.

Main Results:

• Nrf2 plays a dual role in cancer, acting as a tumor suppressor in early stages and a promoter in later stages.
• Constitutive Nrf2 activation promotes cancer cell survival, proliferation, and resistance to chemotherapy and radiotherapy.
• Several small molecules targeting Nrf2 have been identified, with ongoing research into their mechanisms.

Conclusions:

• Inhibiting Nrf2 is a viable therapeutic strategy for cancers with aberrant Nrf2 activation.
• Targeting Nrf2 may overcome chemo- and radio-resistance in cancer treatment.
• Further development of novel Nrf2 inhibitors is crucial for advancing cancer therapy.