Clinical utility of liquid biopsy-based companion diagnostics in the non-small-cell lung cancer treatment

Abstract

Recently, technological advances in the detection and biological characterization of circulating tumor DNA (ctDNA) have enabled the implementation of liquid biopsy testing into clinical practice. Methods for analysis of liquid biopsies have rapidly evolved over the past few years and have continued to advance, thus providing details about tumor biological characteristics such as tumor progression, metastasis, tumor heterogeneity, genomic mutation profile, clonal evolution, etc. In tandem with technological advances, the implementation of liquid biopsy in routine clinical settings has proceeded. In 2016, the Food and Drug Administration (FDA) approved the first ctDNA liquid biopsy test to detect epidermal growth factor receptor (EGFR) gene mutations in patients with non-small-cell lung cancer (NSCLC) as a companion diagnostic for molecular targeted drug of EGFR-tyrosine kinase inhibitor (TKI, EGFR-TKI). More recently, multigene panel assays of liquid biopsy have been approved as companion diagnostics and have been used in routine clinical settings. The estimation of blood tumor mutation burden (bTMB) to predict the efficacy of immune checkpoint inhibitor (ICI) treatment can be one of the promising approaches to liquid biopsy. The next stage of implementation of liquid biopsy for routine clinical settings is for monitoring of ctDNA after surgical treatment to predict prognosis and to detect disease relapse earlier than conventional imaging diagnosis. Its clinical utility is under assessment in several clinical trials. This review introduces recent advances in liquid biopsy methodology, the development of biomarkers, and its clinical utility in the treatment of NSCLC patients.

Keywords: Liquid biopsy; companion diagnostics; genome informatics.