Molecular and clinical disparity of -mutant non-small cell lung cancer (NSCLC) based on histopathological stage and molecular subtypes.
[BACKGROUND] While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a cornerstone of therapy for advanced -mutant non-small cell lung cancer (NSCLC), resistance remains a
APA
Yoon D, Lee JW, et al. (2026). Molecular and clinical disparity of -mutant non-small cell lung cancer (NSCLC) based on histopathological stage and molecular subtypes.. Translational lung cancer research, 15(3), 50. https://doi.org/10.21037/tlcr-2025-1-1354
MLA
Yoon D, et al.. "Molecular and clinical disparity of -mutant non-small cell lung cancer (NSCLC) based on histopathological stage and molecular subtypes.." Translational lung cancer research, vol. 15, no. 3, 2026, pp. 50.
PMID
41982701
Abstract
[BACKGROUND] While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a cornerstone of therapy for advanced -mutant non-small cell lung cancer (NSCLC), resistance remains a major clinical challenge. The genomic landscape of early-stage (ES) -mutant NSCLC and its evolution to advanced-stage (AS) disease is not fully understood. This study aimed to characterize the molecular disparities between ES and AS -mutant NSCLC and to identify genomic alterations associated with EGFR-TKI treatment outcomes.
[METHODS] We have collected and profiled the complex genomes of 121 ES and 74 AS NSCLCs to determine their molecular and clinical disparities. Furthermore, we analyzed 84 mutant NSCLC patients who were treated with EGFR-TKIs to identify potential molecular correlates that could predict the treatment response within the clinic. Patients were stratified by progression-free survival (PFS) and overall response rate (ORR), and hazard ratio analyses were performed.
[RESULTS] In the study, significant enrichment of mutations in , , , , and was observed in AS tumors, whereas ES tumors predominantly exhibited mutations activating , , and . In the EGFR-TKI cohort, poor responders harbored frequent mutations in , , and , and these were associated with worse clinical outcomes. Conversely, favorable responders showed enrichment of , , , and mutations. and were linked to increased hazard, while and mutations correlated with improved prognosis.
[CONCLUSIONS] Given the growing importance of biomarker-driven treatment in the field of oncology, our results collectively open up new therapeutic opportunities for ES NSCLC patients.
[METHODS] We have collected and profiled the complex genomes of 121 ES and 74 AS NSCLCs to determine their molecular and clinical disparities. Furthermore, we analyzed 84 mutant NSCLC patients who were treated with EGFR-TKIs to identify potential molecular correlates that could predict the treatment response within the clinic. Patients were stratified by progression-free survival (PFS) and overall response rate (ORR), and hazard ratio analyses were performed.
[RESULTS] In the study, significant enrichment of mutations in , , , , and was observed in AS tumors, whereas ES tumors predominantly exhibited mutations activating , , and . In the EGFR-TKI cohort, poor responders harbored frequent mutations in , , and , and these were associated with worse clinical outcomes. Conversely, favorable responders showed enrichment of , , , and mutations. and were linked to increased hazard, while and mutations correlated with improved prognosis.
[CONCLUSIONS] Given the growing importance of biomarker-driven treatment in the field of oncology, our results collectively open up new therapeutic opportunities for ES NSCLC patients.