Potential Applications of NRF2 Inhibitors in Cancer Therapy

The NRF2/KEAP1 pathway represents one of the most important cell defense mechanisms against exogenous or endogenous stressors. Indeed, by increasing the expression of several cytoprotective genes, the transcription factor NRF2 can shelter cells and tissues from multiple sources of damage including x...

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Main Authors: Emiliano Panieri, Luciano Saso
Format: Article
Language:English
Published: Hindawi Limited 2019-01-01
Series:Oxidative Medicine and Cellular Longevity
Online Access:http://dx.doi.org/10.1155/2019/8592348
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spelling doaj-c85e2e5fff8b4117b8b723e504ede2602020-11-24T21:50:29ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942019-01-01201910.1155/2019/85923488592348Potential Applications of NRF2 Inhibitors in Cancer TherapyEmiliano Panieri0Luciano Saso1Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University, P.le Aldo Moro 5, 00185 Rome, ItalyThe NRF2/KEAP1 pathway represents one of the most important cell defense mechanisms against exogenous or endogenous stressors. Indeed, by increasing the expression of several cytoprotective genes, the transcription factor NRF2 can shelter cells and tissues from multiple sources of damage including xenobiotic, electrophilic, metabolic, and oxidative stress. Importantly, the aberrant activation or accumulation of NRF2, a common event in many tumors, confers a selective advantage to cancer cells and is associated to malignant progression, therapy resistance, and poor prognosis. Hence, in the last years, NRF2 has emerged as a promising target in cancer treatment and many efforts have been made to identify therapeutic strategies aimed at disrupting its prooncogenic role. By summarizing the results from past and recent studies, in this review, we provide an overview concerning the NRF2/KEAP1 pathway, its biological impact in solid and hematologic malignancies, and the molecular mechanisms causing NRF2 hyperactivation in cancer cells. Finally, we also describe some of the most promising therapeutic approaches that have been successfully employed to counteract NRF2 activity in tumors, with a particular emphasis on the development of natural compounds and the adoption of drug repurposing strategies.http://dx.doi.org/10.1155/2019/8592348
collection DOAJ
language English
format Article
sources DOAJ
author Emiliano Panieri
Luciano Saso
spellingShingle Emiliano Panieri
Luciano Saso
Potential Applications of NRF2 Inhibitors in Cancer Therapy
Oxidative Medicine and Cellular Longevity
author_facet Emiliano Panieri
Luciano Saso
author_sort Emiliano Panieri
title Potential Applications of NRF2 Inhibitors in Cancer Therapy
title_short Potential Applications of NRF2 Inhibitors in Cancer Therapy
title_full Potential Applications of NRF2 Inhibitors in Cancer Therapy
title_fullStr Potential Applications of NRF2 Inhibitors in Cancer Therapy
title_full_unstemmed Potential Applications of NRF2 Inhibitors in Cancer Therapy
title_sort potential applications of nrf2 inhibitors in cancer therapy
publisher Hindawi Limited
series Oxidative Medicine and Cellular Longevity
issn 1942-0900
1942-0994
publishDate 2019-01-01
description The NRF2/KEAP1 pathway represents one of the most important cell defense mechanisms against exogenous or endogenous stressors. Indeed, by increasing the expression of several cytoprotective genes, the transcription factor NRF2 can shelter cells and tissues from multiple sources of damage including xenobiotic, electrophilic, metabolic, and oxidative stress. Importantly, the aberrant activation or accumulation of NRF2, a common event in many tumors, confers a selective advantage to cancer cells and is associated to malignant progression, therapy resistance, and poor prognosis. Hence, in the last years, NRF2 has emerged as a promising target in cancer treatment and many efforts have been made to identify therapeutic strategies aimed at disrupting its prooncogenic role. By summarizing the results from past and recent studies, in this review, we provide an overview concerning the NRF2/KEAP1 pathway, its biological impact in solid and hematologic malignancies, and the molecular mechanisms causing NRF2 hyperactivation in cancer cells. Finally, we also describe some of the most promising therapeutic approaches that have been successfully employed to counteract NRF2 activity in tumors, with a particular emphasis on the development of natural compounds and the adoption of drug repurposing strategies.
url http://dx.doi.org/10.1155/2019/8592348
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