Recent advances in liquid biopsy for precision oncology: emerging biomarkers and clinical applications in lung cancer

Abstract

Lung Cancer (LC) remains the leading cause of cancer-related mortality. While Tissue Biopsy (TB) remains the gold standard for molecular profiling, its invasiveness and inability to provide real-time monitoring have led to the adoption of Liquid Biopsy (LB) as a minimally invasive alternative. By analyzing different circulating analytes such as cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), Circulating Tumor Cells (CTCs), Extracellular Vesicles (EVs), and Tumor-Educated Platelets (TEPs), LB offers a dynamic approach to assessing tumor heterogeneity, Minimal Residual Disease (MRD), and treatment resistance. Recent clinical trials have underscored their role in guiding therapy decisions and monitoring treatment response. In early-stage disease, several Randomized Clinical Trials (RCTs) have shown that ctDNA clearance predicts survival benefits in patients receiving neoadjuvant or perioperative Immune Checkpoint Inhibitors (ICIs). Additionally, adjuvant RCTs have confirmed the ctDNA prognostic role in post-surgical relapse risk assessment. Despite its transformative potential, challenges such as assay standardization, sensitivity limitations in early-stage disease, and regulatory barriers remain. As ongoing research continues to validate its clinical utility, LB is poised to become an indispensable tool in the precision management of LC.

Keywords: MRD; NSCLC; ctDNA; drug resistance; early detection; liquid biopsy; perioperative; precision medicine.