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Author Spotlight: Advancing Reproductive Immunology with a Protocol for the Quantitative Evaluation of Endometrial Immune Cells
Published on: October 13, 2023
Targeting the NRF2/KEAP1 pathway in cervical and endometrial cancers
Giovanni Tossetta1, Daniela Marzioni2
1Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126, Ancona, Italy; Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Università Politecnica delle Marche, Salesi Hospital, Azienda Ospedaliero Universitaria, 60126, Ancona, Italy.
Abstract:
Cervical and endometrial cancers are among the most dangerous gynaecological malignancies, with high fatality and recurrence rates due to frequent diagnosis at an advanced stage and chemoresistance onset. The NRF2/KEAP1 signalling pathway plays an important role in protecting cells against oxidative damage due to increased reactive oxygen species (ROS) levels. NRF2, activated by ROS, induces the expression of antioxidant enzymes such as heme oxygenase, catalase, glutathione peroxidase and superoxide dismutase which neutralize ROS, protecting cells against oxidative stress damage. However, activation of NRF2/KEAP1 signalling in cancer cells results in chemoresistance, inactivating drug-mediated oxidative stress and protecting cancer cells from drug-induced cell death. We review the literature on the role of the NRF2/KEAP1 pathway in cervical and endometrial cancers, with a focus on the expression of its components and downstream genes. We also examine the role of the NRF2/KEAP1 pathway in chemotherapy resistance and how this pathway can be modulated by natural and synthetic modulators.
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