“Keaping” an Eye on the NRF2 Signature Score: Expanding Its Applicability in Lung Cancer

Dysregulation of the KEAP1/NRF2 pathway is a common occurrence in NSCLC and holds clinical significance in various aspects, including immune microenvironment modulation, metabolic reprogramming, genomic stability, metastatic potential, and treatment resistance. 1 Xu K. Ma J. Hall S.R.R. Peng R.W. Yang H. Yao F. Battles against aberrant KEAP1-NRF2 signaling in lung cancer: intertwined metabolic and immune networks. Theranostics. 2023; 13: 704-723 Crossref PubMed Scopus (6) Google Scholar The KEAP1/NRF2 pathway exhibits intricate regulation by multiple upstream molecules, surpassing the conventional KEAP1 or NFE2L2 mutations. 1 Xu K. Ma J. Hall S.R.R. Peng R.W. Yang H. Yao F. Battles against aberrant KEAP1-NRF2 signaling in lung cancer: intertwined metabolic and immune networks. Theranostics. 2023; 13: 704-723 Crossref PubMed Scopus (6) Google Scholar KEAP1/NFE2L2 Pathway Signature Outperforms KEAP1/NFE2L2 Mutation Status and Reveals Alternative Pathway-Activating Mutations in NSCLCJournal of Thoracic OncologyVol. 18Issue 11PreviewActivation of the antioxidant KEAP1/NFE2L2 (NRF2) pathway leads to increased glutamine dependence and an aggressive phenotype in NSCLC. Because this pathway has been explored as a clinical target, we developed a transcriptomic signature for identifying KEAP1/NFE2L2-activated tumors. Full-Text PDF Open AccessIn ResponseJournal of Thoracic OncologyVol. 18Issue 11PreviewWe thank Yang et al. for their thoughtful comments and suggestions and for the opportunity to clarify the intended use of the K1N2 score in more detail. Full-Text PDF