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Controversy about pharmacological modulation of Nrf2 for cancer therapy

Milković, Lidija; Žarković, Neven; Saso, Luciano (2017) Controversy about pharmacological modulation of Nrf2 for cancer therapy. Redox Biology, 12 . pp. 727-732. ISSN 2213-2317

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Abstract

Conventional anticancer therapies such as radiotherapy and chemotherapies are associated with oxidative stress generating reactive oxygen species (ROS) and reactive aldehydes like 4-hydroxynonenal in cancer cells that govern them to die. The main mechanism activated due to exposure of the cell to these reactive species is the Nrf2-Keap1 pathway. Although Nrf2 was firstly perceived as a tumor suppressor that inhibits tumor initiation and cancer metastasis, more recent data reveal its role also as a pro-oncogenic factor. Discovery of the upregulation of Nrf2 in different types of cancer supports such undesirable pathophysiological roles of Nrf2. The upregulation of Nrf2 leads to activation of cytoprotective genes thus helping malignant cells to withstand high levels of ROS and to avoid apoptosis, eventually becoming resistant to conventional anticancer therapy. Therefore, new treatment strategies are needed for eradication of cancer and in this review, we will explore two opposing approaches for modulation of Nrf2 in cancer treatments.

Item Type: Article
Uncontrolled Keywords: cancer; nrf2 ; oxidative stress; cancer therapy; growth regulation; 4-hydroxynonenal
Subjects: BIOMEDICINE AND HEALTHCARE
BIOMEDICINE AND HEALTHCARE > Pharmacy > Medical Biochemistry
Divisions: Division of Molecular Medicine
Projects:
Project titleProject leaderProject codeProject type
Lipidi, slobodni radikali i njihovi glasnici u integrativnoj onkologiji-Neven ZARKOVIC098-0982464-2519MZOS
Depositing User: Lidija Milković
Date Deposited: 09 Aug 2017 10:04
Last Modified: 09 Aug 2017 10:04
URI: http://fulir.irb.hr/id/eprint/3518
DOI: 10.1016/j.redox.2017.04.013

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