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Updated: Feb 3, 2026

Exosomal miRNA Analysis in Non-small Cell Lung Cancer NSCLC Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
Published on: May 27, 2016
Importance of the Keap1-Nrf2 pathway in NSCLC: Is it a possible biomarker?
1Department of Biochemistry and Environmental Medicine, National Institute of Respiratory Diseases, Mexico City 14080, Mexico.
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.
Insights
Constitutive Nrf2 activation, often due to Keap1 mutations, predicts chemotherapy response in non-small cell lung cancer (NSCLC). Targeting this pathway may improve survival for advanced NSCLC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
- Chemotherapy resistance is a major challenge in treating advanced NSCLC.
- Alterations in the Keap1-Nrf2 pathway are common in NSCLC.
Purpose of the Study:
- To review the role of the Keap1-Nrf2 pathway in NSCLC chemotherapy resistance.
- To explore the potential of Nrf2 as a biomarker for predicting treatment response.
- To evaluate Nrf2 inhibitors as a therapeutic strategy for NSCLC.
Main Methods:
- Comparative genomic analyses of NSCLC tumors.
- Review of literature on Keap1-Nrf2 pathway function and clinical implications.
- Analysis of Nrf2 activation as a predictor of chemotherapy efficacy.
Main Results:
- Frequent disruptions in the Keap1-Nrf2 pathway, particularly Keap1 mutations, are observed in NSCLC.
- Constitutive Nrf2 activation is linked to chemotherapy resistance.
- Nrf2 mutations are less common than Keap1 mutations.
Conclusions:
- The Keap1-Nrf2 pathway is crucial in regulating cellular resistance to chemotherapy.
- Constitutive Nrf2 activation can serve as a predictive biomarker for chemotherapy response in NSCLC.
- Nrf2 inhibitors represent a potential therapeutic avenue for NSCLC patients with Keap1-Nrf2 mutations.
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