Implications of NRF2 in Cancer Progression and Therapeutics

Abstract

Cancer is a multifactorial pathological condition that involves mutational changes with abandoned cellular proliferation. Various studies related to cancer have demonstrated the role of oxidative stress as one of the key contributor in its progression. It can lead to activation of various transcription factors and NRF2 emerges as a chief regulator. NRF2 is responsible in modulating various oxidative and electrophilic stress pathways by stimulating the expression of a range of antioxidant response element (ARE)-dependent genes. Since its discovery, it has been considered as a cytoprotective factor and its activators have been in trials in various phases for cancer prevention and other therapies associated with oxidative stress; however, constitutive expression of NRF2 is committed to the proliferation, survival, and growth of cancerous cells, along with resistance to chemotherapeutic agents in many types of tumors. In the present compilation, we provide an outline of the NRF2 signaling pathway and confer its role in malignancy. We have addressed the effects of NRF2 and its downstream targets in various types of cancer pathologies and also discuss various pharmacological inhibitors of NRF2 in different stages of clinical development.