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Journal Article
Review
The mechanistic insights of the antioxidant Keap1-Nrf2 pathway in oncogenesis: a deadly scenario.
Medical Oncology 2023 July 23
The Nuclear factor erythroid 2-related factor 2 (Nrf2) protein has garnered significant interest due to its crucial function in safeguarding cells and tissues. The Nrf2 protein is crucial in preserving tissue integrity by safeguarding cells against metabolic, xenobiotic and oxidative stress. Due to its various functions, Nrf2 is a potential pharmacological target for reducing the incidence of diseases such as cancer. However, mutations in Keap1-Nrf2 are not consistently favored in all types of cancer. Instead, they seem to interact with specific driver mutations of tumors and their respective tissue origins. The Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 pathway mutations are a powerful cancer adaptation that utilizes inherent cytoprotective pathways, encompassing nutrient metabolism and ROS regulation. The augmentation of Nrf2 activity elicits significant alterations in the characteristics of neoplastic cells, such as resistance to radiotherapy and chemotherapy, safeguarding against apoptosis, heightened invasiveness, hindered senescence, impaired autophagy and increased angiogenesis. The altered activity of Nrf2 can arise from diverse genetic and epigenetic modifications that instantly impact Nrf2 regulation. The present study aims to showcase the correlation between the Keap1-Nrf2 pathway and the progression of cancers, emphasizing genetic mutations, metabolic processes, immune regulation, and potential therapeutic strategies. This article delves into the intricacies of Nrf2 pathway anomalies in cancer, the potential ramifications of uncontrolled Nrf2 activity, and therapeutic interventions to modulate the Keap1-Nrf2 pathway.
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