Abstract
Nrf2, a key cellular regulator, plays a complex and multifaceted role in both protecting healthy cells and potentially promoting disease progression. This chapter delves into the intricate mechanisms by which Nrf2 exerts its protective effects, including combating carcinogens, maintaining cellular integrity, and inducing controlled cell death under severe stress. However, the chapter also explores the “dark side” of Nrf2, where its activity in cancer cells can contribute to chemoresistance, adaptation, and growth, hindering effective treatment. The chapter further investigates current research avenues for harnessing Nrf2’s potential for therapeutic benefit. Strategies for both activation and inhibition are explored, highlighting the importance of context-dependent effects, balancing protection and potential harm, and minimizing off-target effects. Promising new directions, such as developing tissue-specific modulators, identifying predictive biomarkers, and combining Nrf2 modulators with other therapeutic approaches, are also discussed. By understanding Nrf2’s complex and context-dependent roles, we can pave the way for the development of safer and more effective therapeutic strategies that leverage its beneficial effects while mitigating its potential drawbacks in various diseases.