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Importance of the Keap1-Nrf2 Pathway in NSCLC: Is It a Possible Biomarker?

Overview
Journal Biomed Rep
Specialty Biochemistry
Date 2018 Oct 23
PMID 30345037
Citations 23
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Abstract

Worldwide, lung cancer remains the most common cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for 85% of all diagnosed lung cancer cases. Chemotherapy is considered the standard of care for patients with advanced NSCLC; however, the tumors can develop mechanisms that inactivate these drugs. Comparative genomic analyses have revealed that disruptions in the kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid-2-related factor-2 (Nrf2) pathway are frequent in NSCLC, although Nrf2 mutations occur less frequently than Keap1 mutations. As the Keap1-Nrf2 pathway appears to be a primary regulator of key cellular processes that aid to resist the action of chemotherapy drugs, the clinical implementation of Nrf2 inhibitors in patients with advanced NSCLC may be a useful therapeutic approach for patients harboring KEAP1-NRF2 mutations. The aim of the present review was to highlight findings of how constitutive Nrf2 activation may be a specific biomarker for predicting patients most likely to benefit from classical chemotherapy drugs, overall improving patient survival rate.

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References
1.
Jacobsen K, Bertran-Alamillo J, Molina M, Teixido C, Karachaliou N, Pedersen M . Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer. Nat Commun. 2017; 8(1):410. PMC: 5583255. DOI: 10.1038/s41467-017-00450-6. View

2.
Abed D, Goldstein M, Albanyan H, Jin H, Hu L . Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents. Acta Pharm Sin B. 2015; 5(4):285-99. PMC: 4629420. DOI: 10.1016/j.apsb.2015.05.008. View

3.
Shibata T, Ohta T, Tong K, Kokubu A, Odogawa R, Tsuta K . Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci U S A. 2008; 105(36):13568-73. PMC: 2533230. DOI: 10.1073/pnas.0806268105. View

4.
. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012; 489(7417):519-25. PMC: 3466113. DOI: 10.1038/nature11404. View

5.
Nioi P, Nguyen T . A mutation of Keap1 found in breast cancer impairs its ability to repress Nrf2 activity. Biochem Biophys Res Commun. 2007; 362(4):816-21. DOI: 10.1016/j.bbrc.2007.08.051. View