The 2025 lung cancer landscape: advances in screening, molecular taxonomy and therapeutic strategy: a narrative review.

Abstract

Background and objective: In 2025, lung cancer research advanced rapidly across the disease continuum, from population-level risk assessment and screening to mechanistic studies of early carcinogenesis and therapeutic innovation in perioperative and metastatic settings. A key shift moved beyond a smoking-centred paradigm toward a multidimensional risk framework reflecting the growing burden among never-smokers and the roles of air pollution, occupational exposures, and systemic metabolic-inflammatory states. This narrative review aims to synthesize influential 2025 evidence across prevention, diagnosis, treatment, and survivorship, and to identify convergent themes and translational gaps relevant to clinical practice and policy.

Methods: We performed a narrative synthesis of influential lung cancer studies published in major international journals in 2025. Evidence was organized along a clinically oriented pathway spanning carcinogenesis and screening, precision diagnosis, treatment optimization in resectable and advanced disease, and survivorship, emphasizing practice-informing trials, high-impact translational research, and implementation-relevant technologies.

Key content and findings: Lineage tracing, single-cell and spatial omics, and evolutionary inference refined concepts of field cancerization, clonal selection, and copy-number-driven fitness. In small-cell lung cancer, evidence further supported neuronal coupling and synapse-like programs as potentially tractable vulnerabilities. Clinically, low-dose computed tomography (CT) strategies and data-informed nodule thresholds aimed to balance under-detection against over-surveillance harms. In diagnostics, artificial intelligence (AI) models increasingly inferred molecular features from routine histopathology ("virtual molecular testing") and should be regarded as decision support requiring prospective validation, population calibration, and explicit failure-mode reporting. Multimodal approaches integrating imaging with circulating tumor DNA (ctDNA) improved feasibility in tissue-limited settings, but clinical utility remains contingent on assay standardization and pathway-level implementation. In resectable disease, longer follow-up consolidated neoadjuvant chemo-immunotherapy for selected patients, while ctDNA kinetics emerged as a candidate biomarker for response-adaptive escalation and de-escalation. In advanced non-small cell lung cancer (NSCLC), phase III evidence for antibody-drug conjugates and bispecific antibodies began reshaping sequencing, while highlighting challenges in toxicity, access, affordability, and immature overall survival in several programs.

Conclusions: The 2025 landscape reflects coordinated progress in risk conceptualization, biology, diagnostics, and therapeutics, yet gaps in validation, standardization, and real-world deliverability persist. Priorities include prospective evaluation of AI- and ctDNA-enabled pathways, toxicity-informed sequencing, and equitable implementation aligned with health-system capacity.