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Cancer Genomics and Diagnostics / Lung Cancer Treatments and Mutations / Lung Cancer Diagnosis and Treatment · Journal article
Genes · September 7, 2026
A consensus or society position rather than new primary data.
This is a structured narrative review of 99 studies published 2015–2026 that synthesizes evidence on molecular biomarkers, diagnostic methods, and resistance mechanisms in NSCLC precision oncology. It proposes a novel three-tiered conceptual framework for acquired resistance (genetic, cellular plasticity, and microenvironmental) and concludes that precision oncology is evolving toward dynamic integration of diagnostics and continuous resistance monitoring, though the review does not report new primary trial data or quantitative effect sizes.
Structured narrative literature review. Literature addressing NSCLC precision oncology; no specific patient cohort characteristics reported.. Intervention: Molecular diagnostics (NGS, liquid biopsy) and targeted therapies directed at actionable biomarkers (EGFR, ALK, ROS1, KRAS, RET, MET, HER2, NTRK) in NSCLC. Compared with: Conventional chemotherapy (referenced as comparator in qualitative assessment but not quantitatively analyzed in the abstract).
Actionable biomarkers identified include EGFR, ALK, ROS1, KRAS, RET, MET, HER2, NTRK alterations, and emerging targets such as NRG1 fusions NGS emerged as the cornerstone of comprehensive molecular profiling; liquid biopsy enabled longitudinal monitoring of tumor dynamics and resistance development Acquired resistance mechanisms were organized into three tiers: target-centric genetic evolution (Tier 1), cellular plasticity and intratumoral heterogeneity (Tier 2), and non-genetic/microenvironmental adaptation (Tier 3)
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
Clinicians and researchers should use this review as a reference framework for understanding current actionable biomarkers, diagnostic strategies (NGS and liquid biopsy), and the emerging three-tiered model of resistance mechanisms to guide molecular reassessment at progression and inform adaptive treatment strategies. The framework is intended to support precision medicine decision-making but represents synthesis of existing evidence rather than new empirical results.
A structured narrative review synthesizing evidence from 99 foundational studies and clinical documents to provide organized guidance on molecular biomarkers, diagnostic methods, and resistance mechanisms in NSCLC precision oncology, rather than reporting original trial data.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians and researchers should use this review as a reference framework for understanding current actionable biomarkers, diagnostic strategies (NGS and liquid biopsy), and the emerging three-tiered model of resistance mechanisms to guide molecular reassessment at progression and inform adaptive treatment strategies. The framework is intended to support precision medicine decision-making but represents synthesis of existing evidence rather than new empirical results.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background: Precision oncology has significantly transformed the management of non-small cell lung cancer (NSCLC) through the integration of molecular diagnostics, targeted therapies, and biomarker-driven treatment selection. Advances in next-generation sequencing (NGS) and liquid biopsy have improved the identification of actionable molecular alterations and enabled dynamic monitoring of tumor evolution. Objective: To provide a structured narrative review of current evidence regarding actionable molecular biomarkers, diagnostic methodologies, targeted therapies, and future directions in NSCLC precision oncology, with a specific focus on conceptualizing acquired resistance mechanisms. Methods: A structured narrative literature review was conducted by searching PubMed and Google Scholar for English-language studies published between 2015 and 2026. Eligible publications included clinical trials, cohort studies, translational research, reviews, and clinical guidelines addressing molecular profiling, targeted treatments, diagnostic approaches, and resistance mechanisms in NSCLC. Results: A total of 99 foundational studies and clinical documents were analyzed. Key actionable biomarkers included EGFR (Epidermal Growth Factor Receptor), ALK (Anaplastic Lymphoma Kinase), ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase), KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog), RET (Rearranged during Transfection), MET (Mesenchymal–Epithelial Transition Factor), HER2 (Human Epidermal Growth Factor Receptor 2) and NTRK (Neurotrophic Tyrosine Receptor Kinase) alterations, along with emerging targets such as NRG1 (Neuregulin 1) fusions. NGS emerged as the cornerstone of comprehensive molecular profiling, while liquid biopsy enabled longitudinal monitoring of tumor dynamics and resistance development. To organize the biological complexity of treatment failure, acquired resistance mechanisms were categorized into a three-tiered conceptual framework: target-centric genetic evolution (Tier 1), cellular plasticity and intratumoral heterogeneity (Tier 2), and non-genetic/microenvironmental adaptation (Tier 3). Targeted therapies significantly improved clinical outcomes compared with conventional chemotherapy; however, acquired resistance remained a major challenge across all tiers. Conclusions: Precision oncology in NSCLC is evolving from a biomarker-focused approach toward a dynamic framework integrating molecular diagnostics, targeted therapies, and continuous resistance monitoring. The proposed three-tiered resistance framework provides a structured basis for understanding treatment failure, guiding molecular reassessment at progression, and informing future adaptive therapeutic strategies to improve long-term patient outcomes.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.