In This Issue/Research Watch/News-in-Brief/News from 002the IASLC Tobacco Control Committee

Abstract

The epidermal stress response pathway is frequently dysregulated in NSCLC. However, the clinical relevance of these alterations remains unclear. To address this issue, the authors studied two of the genes involved in this pathway (kelch like ECH associated protein 1 gene [KEAP1] and nuclear factor erythroid 2 like 2 gene [NFE2L2]) in 88 advanced NSCLC patients by amplicon-based next-generation sequencing. Lung adenocarcinomas with mutations in the KEAP1-NFE2L2 pathway had a significantly shorter progression-free survival and overall survival when compared to wild-type tumors. This observation was further validated in two large independent cohorts (n¼1256 and n¼162, respectively). The authors also observed that the mutations in the KEAP1-NFE2L2 pathway and EGFR/anaplastic lymphoma kinase (ALK) alterations were mutually exclusive. The results of this study indicate that KEAP1/ NFE2L2 mutations may identify a subset of chemotherapy-resistant and rapidly progressing tumors among EGFR/ ALK-negative lung adenocarcinomas, whose outcome is already compromised due to the lack of targetable molecular alterations. Effective treatment options need to be identified for this subset of patients with extremely adverse outcome.