Cancer Treat Res Commun. 2026 Oct 1;49:101463. doi: 10.1016/j.ctarc.2026.101463. Online ahead of print.

ABSTRACT

Liquid biopsy has transformed the management of non-small cell lung cancer (NSCLC). However, current plasma-based approaches face inherent limitations in early-stage and low-burden disease, where tumour-derived DNA fractions are frequently below reliable detection thresholds. As lung cancer care shifts toward earlier detection and minimal residual disease assessment, these constraints expose a critical gap in tumour-proximal molecular sampling. This has prompted growing interest in organ-specific liquid biopsy strategies designed to interrogate biological compartments closer to the site of tumour origin. Exhaled breath condensate (EBC), a non-invasive and lung-derived matrix containing airway lining fluid, represents a biologically rational candidate for such an approach. Emerging translational studies demonstrate the feasibility of detecting tumour-associated genomic alterations and nucleic acids within EBC, suggesting potential utility in early detection, molecular profiling, and longitudinal monitoring. However, substantial challenges remain, including pre-analytical standardisation, analytical validation, and prospective clinical evaluation. This narrative review examines the conceptual rationale for lung-specific liquid biopsy, summarises the evolving evidence supporting EBC, and outlines critical and translational steps required to determine whether EBC can become an integral component of lung cancer diagnostics.

PMID:42822136 | DOI:10.1016/j.ctarc.2026.101463