J Thorac Dis. 2026 Apr 30;18(4):415. doi: 10.21037/jtd-2026-1-0025. Epub 2026 Apr 24.

ABSTRACT

BACKGROUND AND OBJECTIVE: Circulating tumor cells (CTCs) are malignant cells shed into blood that enable noninvasive, longitudinal assessment of lung cancer. Increasing evidence frames CTCs within a circulating tumor microenvironment (cTME) and broader circulating tumor-associated cell (CTAC) ecosystems that include multicellular clusters and circulating tumor endothelial cells (CTECs). We summarize definitions, detection approaches, and clinical applications of CTC-centered liquid biopsy in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

METHODS: A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Google Scholar using the terms "non-small cell lung cancer", "small cell lung cancer", and "circulating tumor cells". Relevant clinical, basic, and translational studies were selected and synthesized to outline current knowledge and future directions.

KEY CONTENT AND FINDINGS: CTCs can be enriched by immunoaffinity, size, or microfluidic platforms, enabling enumeration and downstream profiling. In both NSCLC and SCLC, CTC positivity and higher burden are associated with worse survival, with the strongest effects in SCLC and with circulating tumor emboli (CTE). Serial monitoring provides early signals of response or failure; and post-treatment supports minimal residual disease (MRD) detection and relapse prediction. Molecular and phenotypic profiling enables driver and resistance tracking, including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), while CTECs may add vascular and immune-relevant information.

CONCLUSIONS: CTC-based assays have the potential to complement imaging and tissue biopsy across screening research, prognostication, therapeutic monitoring, MRD assessment, and personalized care. Clinical translation requires standardized preanalytical workflows, harmonized thresholds, and prospective trials testing CTC-guided management.

PMID:42182710 | PMC:PMC13190041 | DOI:10.21037/jtd-2026-1-0025