Liquid Biopsy by Next-Generation Sequencing: a Multimodality Test for Management of Cancer

Abstract

Purpose of review: While liquid biopsy is still relatively a new concept, the advent of next-generation sequencing (NGS) technologies has recently generated a revolution in the field and will be the focus of this review.

Recent findings: Circulating tumor DNA (ctDNA) derives from tumor cells and provides information about the genetic alterations of tumors. However, ctDNA concentration in plasma can be below the level of detection by conventional methods; therefore, screening for actionable genetic information is challenging. Clinical trials exploring targeted and untargeted sequencing to improve the outcomes of ctDNA detection are showing promising results, having reached a limit of detection as low as 0.001% of ctDNA in a background of normal circulating DNA. Most of the challenges related to the sensitivity of detection of ctDNA have been defeated by dint of NGS-based approaches. Despite all the efforts, these methods are still expensive, time-consuming, and require advanced skills for appropriate interpretation. Nevertheless, the technology is rapidly improving, and the expectations for the implementation of liquid biopsy into the clinical practice in the near future are high.

Keywords: Circulating tumor DNA; Liquid biopsy; Next-generation sequencing; Targeted sequencing; Untargeted sequencing.