Nrf2 is a potential therapeutic target in radioresistance in human cancer

Zhou, Suna; Ye, Wenguang; Shao, Qing; Zhang, Mingxin; Liang, Jun

doi:10.1016/j.critrevonc.2013.09.001

Cited by 88 publications

(70 citation statements)

References 125 publications

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“…In the context of targeted immunotherapy, recent reports have suggested a role for NRF2 in determining overall treatment response [37, 55, 56]. More specifically, several studies have either suggested direct cross talk of NRF2 and RTK signaling [36], or modulation of NRF2 by the RTK substrates PI3K [57–59] and MAPK [42, 43].…”

Section: Resultsmentioning

confidence: 99%

A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

et al. 2016

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Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2.HER2 targeting by antibodies inhibited growth in association with persistent generation of reactive oxygen species (ROS), glutathione (GSH) depletion, reduction in NRF2 levels and inhibition of NRF2 function in ovarian cancer cell lines. The combination of antibodies produced more potent effects than single antibody alone; downregulated NRF2 substrates by repressing the Antioxidant Response (AR) pathway with concomitant transcriptional inhibition of NRF2. We showed the antibody combination produced increased methylation at the NRF2 promoter consistent with repression of NRF2 antioxidant function, as HDAC and methylation inhibitors reversed such produced transcriptional effects. These findings demonstrate a novel mechanism and role for NRF2 in mediating the response of cancer cells to the combination of Trastuzumab and Pertuzumab and reinforce the importance of NRF2 in drug resistance and as a key anticancer target.

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Section: Resultsmentioning

confidence: 99%

A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

et al. 2016

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“…Several studies have demonstrated the usefulness of targeting Nrf2 for radiosensitization [8][9][10][11]. Similar to antioxidant response, DNA damage response (DDR) also is an important aspect which determines the radiation response of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells

Jayakumar

Pal

Sandur

2015

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…The products of these genes protect cells against oxidative stress. Because of these mechanisms, most cancer cells survive by neutralizing the effects of oxidative stress, and acquire drug and radiation resistance through the Nrf2-Keap1-ARE signaling pathway [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Disturbance of redox status enhances radiosensitivity of hepatocellular carcinoma

Sun¹,

Liu²,

Liu³

et al. 2017

European Journal of Cancer

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Nrf2 is a potential therapeutic target in radioresistance in human cancer

Cited by 88 publications

References 125 publications

A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells

Disturbance of redox status enhances radiosensitivity of hepatocellular carcinoma

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