The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is a master redox switch that regulates the cellular antioxidant response. Activation of the NRF2 pathway is known to exert a wide range of protection against divergent stresses, including intracellular oxidative stress. NRF2 is also able to regulate the expression of macrophage-specific genes (such as macrophage receptor with collagenous structure MARCO), which are not considered as antioxidative stress-response genes, signifying that NRF2 could also inhibit inflammation via reactive oxygen species (ROS) modulation. In cancer, it has been shown that NRF2 activation plays a protective role in the prevention of chemical- and radiation-induced carcinogenesis. Hence, several NRF2 activators are now in clinical trials for cancer treatment. Nonetheless, recent studies have also identified several functions of NRF2 that go beyond its redox-regulating capacities. Prolonged activation of NRF2 in drosophila for example, shortens the lifespan and promotes malignant transformation of human cells.
In addition, overexpression of the NRF2 protein has recently emerged as a potential mechanism of resistance to platinum and other cytotoxic compounds. NRF2 accumulation has been detected in many cancers, where it has been proven to act as an oncogene. It could limit to an acceptable level the accumulation of ROS produced in excess by the mitochondrial respiratory chain in cancer cells with high metabolic activity, allowing survival of hypermetabolic and proliferative cancer cells. NRF2 also promotes metabolic activities that support cell proliferation. There is therefore, a growing interest in the relation between NRF2 and cancer, and the identification of novel approaches targeting the NRF2 pathway to prevent and/or treat cancer. Many NRF2 inducers are electrophiles and activate NRF2 by modifying KEAP1 cysteine residues to permit NRF2 dissociation and stabilization. However, these inducers can also react with other molecules.
In this Research Topic, we aim to focus on the effect of NRF2 modulation in cancer, and on innovative therapies involving these modulators, whether alone or in combination with other therapies for cancer. By exploring the most recent advances and discoveries in this field, this Research Topic aims to broaden our understanding on the use of NRF2 modulators to treat different types of cancer. We welcome the submission of Original Research, Clinical Trial, Case Report and Review articles presenting studies on animal tumor models and/or human patients affected by cancer and involving the use of compounds that control the NRF2 pathway. The topics to be covered in this Research Topic include but not limited to:
1) Novel therapeutic approaches involving the use of NRF2 modulators to treat cancer
2) Covalent modification/succination of NRF2, KEAP1, and other cystine-rich NRF2 interacting partners; for anti-cancer activity
3) Modulation of antioxidant pathways
4) Modulation of cytokine production and induction of apoptosis in certain immune cell subsets
5) Targeting of intracellular GSH in cancer
6) The effect of NRF2 modulator in malignant versus non-malignant cells
7) Sensitizing cancer cells to therapy
8) Targeting of innate lymphoid cells
Important Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is a master redox switch that regulates the cellular antioxidant response. Activation of the NRF2 pathway is known to exert a wide range of protection against divergent stresses, including intracellular oxidative stress. NRF2 is also able to regulate the expression of macrophage-specific genes (such as macrophage receptor with collagenous structure MARCO), which are not considered as antioxidative stress-response genes, signifying that NRF2 could also inhibit inflammation via reactive oxygen species (ROS) modulation. In cancer, it has been shown that NRF2 activation plays a protective role in the prevention of chemical- and radiation-induced carcinogenesis. Hence, several NRF2 activators are now in clinical trials for cancer treatment. Nonetheless, recent studies have also identified several functions of NRF2 that go beyond its redox-regulating capacities. Prolonged activation of NRF2 in drosophila for example, shortens the lifespan and promotes malignant transformation of human cells.
In addition, overexpression of the NRF2 protein has recently emerged as a potential mechanism of resistance to platinum and other cytotoxic compounds. NRF2 accumulation has been detected in many cancers, where it has been proven to act as an oncogene. It could limit to an acceptable level the accumulation of ROS produced in excess by the mitochondrial respiratory chain in cancer cells with high metabolic activity, allowing survival of hypermetabolic and proliferative cancer cells. NRF2 also promotes metabolic activities that support cell proliferation. There is therefore, a growing interest in the relation between NRF2 and cancer, and the identification of novel approaches targeting the NRF2 pathway to prevent and/or treat cancer. Many NRF2 inducers are electrophiles and activate NRF2 by modifying KEAP1 cysteine residues to permit NRF2 dissociation and stabilization. However, these inducers can also react with other molecules.
In this Research Topic, we aim to focus on the effect of NRF2 modulation in cancer, and on innovative therapies involving these modulators, whether alone or in combination with other therapies for cancer. By exploring the most recent advances and discoveries in this field, this Research Topic aims to broaden our understanding on the use of NRF2 modulators to treat different types of cancer. We welcome the submission of Original Research, Clinical Trial, Case Report and Review articles presenting studies on animal tumor models and/or human patients affected by cancer and involving the use of compounds that control the NRF2 pathway. The topics to be covered in this Research Topic include but not limited to:
1) Novel therapeutic approaches involving the use of NRF2 modulators to treat cancer
2) Covalent modification/succination of NRF2, KEAP1, and other cystine-rich NRF2 interacting partners; for anti-cancer activity
3) Modulation of antioxidant pathways
4) Modulation of cytokine production and induction of apoptosis in certain immune cell subsets
5) Targeting of intracellular GSH in cancer
6) The effect of NRF2 modulator in malignant versus non-malignant cells
7) Sensitizing cancer cells to therapy
8) Targeting of innate lymphoid cells
Important Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
