Genomic profiling and ctDNA integration guide adaptive therapy across NSCLC stages
The study reviews a quarter-century of advances in non-small-cell lung cancer, highlighting how systematic genomic profiling and immune checkpoint inhibitors have transformed treatment across metastatic, locally advanced, and early-stage disease. Investigators note that adjuvant and consolidation targeted therapies now extend precision oncology to EGFR- and ALK-driven early NSCLC, while circulating tumor DNA is emerging as a tool for real-time, adaptive therapy modulation. The review underscores the ongoing need for more discriminating biomarkers to refine treatment sequencing and intensity. For diagnostic laboratories, the synthesis emphasizes the growing clinical utility of comprehensive molecular testing and ctDNA monitoring in guiding lung cancer management.
The original study
A Quarter Century of Transformation: Integrating Molecular Stratification and Immune Modulation Across the Continuum of Non-Small-Cell Lung Cancer.
- Authors
- Nassar AH, Halawi J, Herbst RS
- Journal
- Cancer journal (Sudbury, Mass.)
- Type
- Journal Article, Review
- PMID
- 42497391
Original abstract
Non-small-cell lung cancer (NSCLC) has seen a paradigm shift over the past quarter century driven by systematic molecular characterization, the advent of targeted therapies, the implementation of low-dose CT screening, and the integration of immunotherapy across the disease continuum. Genomic profiling has defined oncogene-addicted subsets for which targeted agents now improve survival in both metastatic and resectable disease, while immune checkpoint inhibitors have displaced chemotherapy as first-line treatment for many patients without actionable drivers and have been incorporated into perioperative and consolidation strategies. Concurrently, adjuvant and consolidation tyrosine kinase inhibition has extended precision oncology into early-stage EGFR- and ALK-driven NSCLC. Here, we review pivotal therapeutic advances across metastatic, locally advanced, and early-stage disease; identify the need for more discriminating markers to refine treatment intensity and sequencing; and outline emerging approaches, including rational upfront combinations and the use of circulating tumor DNA to enable real-time, adaptive modulation of therapy in NSCLC.