Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation

Simple Summary Lung cancer (LCa) remains the leading cause of cancer-related mortality worldwide, with late diagnosis and limited therapeutic approaches still constraining patient's outcome. In recent years, liquid biopsies have significantly improved the disease characterization and brought new insights into LCa diagnosis and management. The integration of microfluidic devices in liquid biopsies have shown promising results regarding circulating biomarkers isolation and analysis and these tools are expected to establish automatized and standardized results for liquid biopsies in the near future. Herein, we review the status of lab-on-a-chip approaches for liquid biopsies in LCa and highlight their current applications for circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) research and clinical validation studies. Despite the intensive efforts dedicated to cancer diagnosis and treatment, lung cancer (LCa) remains the leading cause of cancer-related mortality, worldwide. The poor survival rate among lung cancer patients commonly results from diagnosis at late-stage, limitations in characterizing tumor heterogeneity and the lack of non-invasive tools for detection of residual disease and early recurrence. Henceforth, research on liquid biopsies has been increasingly devoted to overcoming these major limitations and improving management of LCa patients. Liquid biopsy is an emerging field that has evolved significantly in recent years due its minimally invasive nature and potential to assess various disease biomarkers. Several strategies for characterization of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been developed. With the aim of standardizing diagnostic and follow-up practices, microfluidic devices have been introduced to improve biomarkers isolation efficiency and specificity. Nonetheless, implementation of lab-on-a-chip platforms in clinical practice may face some challenges, considering its recent application to liquid biopsies. In this review, recent advances and strategies for the use of liquid biopsies in LCa management are discussed, focusing on high-throughput microfluidic devices applied for CTCs and ctDNA isolation and detection, current clinical validation studies and potential clinical utility.