Liquid biopsy in lung cancer screening: rationale, progress, opportunities and challenges

Lung cancer (LC) remains the leading cause of cancer-related deaths globally. Liquid biopsy offers an accurate and non-invasive screening approach for early detection of LC overcoming the limitations of the current recommended low-dose computed tomography (LDCT). In the current review, we summarized the latest advancements in liquid biopsy for LC screening, evaluating the biological relevance, predictive accuracy, and detection techniques associated with various biomarkers including circulating tumor DNA, proteins, and metabolites. We also addressed the unresolved questions of how to integrate liquid biopsy into routine clinical practice to improve LC outcomes by cost-effective analysis. It is hoped that this study can shed light upon the future development of LC screening methods and provide insights for the potential integration of liquid biopsy into the current clinical practice.