Expanding the Full Potential of Liquid Biopsies for Lung Cancer Patients

In recent years, there has been tremendous therapeutic progress for advanced lung cancer, leading to the identification of a multitude of therapeutic targets and significantly expanding the list of potential target genes to be tested. However, precision oncology requires knowledge of the exact biology of the tumor through sequencing of the cancer genome, which is hampered by limited tissue availability in thoracic malignancies. Liquid biopsy, namely plasma cell-free DNA (cfDNA) analysis, has expanded these opportunities and is now firmly established in the diagnostic algorithm of patients with lung cancer with metastatic disease. However, the full potential of this powerful tool has been largely underexplored. In this issue of Cancer Research, Nair and colleagues provide evidence of the clinical utility of bronchoalveolar lavage (BAL) cfDNA profiling through an ultra-deep next-generation sequencing approach. The study findings support further development of BAL cfDNA analysis for tumor genotyping, besides the current gold standard sources (tissue and plasma), as a complementary tool in patients undergoing diagnostic bronchoscopy for tumor diagnosis and/or rebiopsy, increasing the success rates of genomic analyses. In addition, BAL cfDNA profiling might represent an important diagnostic tool in early-stage lung cancer, outperforming plasma cfDNA in stage I-II and detecting field cancerization signs, potentially identifying tumors before their clinical appearance. Further studies should confirm the full potential of BAL cfDNA profiling in lung cancer and its place in the large family of liquid biopsies. See related article by Nair et al., p. 2838.