Targeting NRF2 and Its Downstream Processes: Opportunities and Challenges

The transcription factor NRF2 coordinates the expression of a vast array of cytoprotective and metabolic genes in response to various stress inputs to restore cellular homeostasis. Transient activation of NRF2 in healthy tissues has been long recognized as a cellular defense mechanism and is critical to prevent cancer initiation by carcinogens. However, cancer cells frequently hijack the protective capability of NRF2 to sustain the redox balance and meet their metabolic requirements for proliferation. Further, aberrant activation of NRF2 in cancer cells confers resistance to commonly used chemotherapeutic agents and radiotherapy. During the last decade, many research groups have attempted to block NRF2 activity in tumors to counteract the survival and proliferative advantage of cancer cells and reverse resistance to treatment In this review, we highlight the role of NRF2 in cancer progression and discuss the past and current approaches to disable NRF2 signaling in tumors.

Automated summary

The transcription factor NRF2 plays a crucial role in regulating cytoprotection and metabolism. Its transient activation in healthy tissues prevents cancer initiation, but cancer cells hijack NRF2 to support their proliferation and develop resistance to treatment. Blocking NRF2 activity in tumors is a promising approach to counteract cancer progression and overcome treatment resistance.