About this Research Topic
Nuclear factor erythroid-2 related factor-2, Nrf2 is a key redox regulator that has been demonstrated to prevent the transformation of normal cells in to cancer cells when activated. However targeted downregulation of Nrf2 expression and/or activity retard proliferation of cancer cells are sensitized to various chemotherapeutic agents and radiation. Several studies using cell lines and clinical biopsies, have demonstrated elevated Nrf2 expression in carcinomas of breast and lung.
Overexpression of Nrf2 can promote cancer cells’ survival, protect cells from toxic reactive oxygen species, increase cell migration and promote drug resistance. Therefore approaches in modulating Nrf2 expression presents a potential pharmacological strategy to prevent and treat cancers. Several naturally occurring and synthetic pharmacological agents have been developed to inhibit the expression of Nrf2 in cancers. For instance brusatol is a well-known Nrf2 inhibitor isolated from Brucea javanica and is known to retard tumor cells growth in vitro and in vivo.
Although several pharmacological agents have been developed to inhibit/mitigate Nrf2 function in malignant cancer cells, to date, no single agent has shown success in clinical trials. The lack of (a) complete understanding of Nrf2 signaling cascade and its role in cancers; (b) information about drug resistance mechanisms; (c) effective pharmacological agents specifically targeting Nrf2 in cancer cells; (d) knowledge about key metabolic processes controlled by Nrf2 in cancer cells; are some of the factors contributing for poor success or failure of anti-Nrf2 agents in clinical trials. Hence, these areas need to be addressed immediately in order to develop effective Nrf2 modulators for the treatment of cancers.
Therefore, this Research Topic primarily emphasizes on receiving Original Research articles, Case Reports, meta-analysis and Review articles focusing on:
- identifying Nrf2 signaling inhibitors
- understanding Nrf2 regulatory mechanisms that are deregulated in cancers. The mechanisms include: (a) glycation; (b) genetic and epigenetic pathways controlling Nrf2; (c) protein-protein interactions; and (d) cellular localization
- developing novel combination therapies to over come drug resistant processes regulated by Nrf2
- in vitro and in vivo studies demonstrating the safety and efficacy of Nrf2 modulators
- approaches that assist in quantifying Nrf2 and its target genes expression and activity in cancers
Keywords: Nrf2, Drug Resistance, Keap1, Glycation, FN3K
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