Next-generation sequencing using liquid biopsy in the care of patients with ALK-rearranged non-small cell lung cancer: a focus on lorlatinib

Next-generation sequencing (NGS) has introduced new applications in the molecular profiling of lung cancer, expanding its use from the essential molecular diagnosis in advanced stages, to disease monitoring and the study of resistance mechanisms to targeted therapies and, most recently, to immunotherapy. Cell-free DNA (cfDNA) NGS is an easily accessible form of liquid biopsy, with the potential of sequencing tumor DNA shed from different metastasis and capturing tumor heterogeneity and tumor clonal evolution during treatment. Lorlatinib, is a novel third-generation ALK inhibitor, and current standard treatment for patients that experience disease progression with crizotinib and a second-generation ALK inhibitor or in the front line setting. Preclinical studies on predictive biomarkers of response and resistance to lorlatinib have been conducted, shedding a light on potential biological mechanisms of primary and acquired resistance to this compound. With the emerging role of cfDNA NGS, ..... READ ARTICLE

Precision Cancer Medicine (PCM) DOI:10.21037/pcm-20-59

Authors: Juan B. Blaquier, Andrés F. Cardona, Alessandro Russo, Christian Rolfo, Gonzalo Recondo

Kirk Smith