Targeting the NRF2/KEAP1 pathway in cervical and endometrial cancers

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.

Automated summary

Cervical and endometrial cancers are highly dangerous gynecological malignancies with high fatality and recurrence rates. The NRF2/KEAP1 pathway is important in protecting cells against oxidative damage. However, its activation in cancer cells leads to chemoresistance. This review discusses the role of the NRF2/KEAP1 pathway in cervical and endometrial cancers, its components and downstream genes, and strategies to modulate this pathway for chemotherapy.