Abstract

The practice of liquid biopsy (LB) has revolutionized the care of patients with metastatic lung cancer. Many oncologists now use this approach in daily practice, applying precise procedures for the detection of activating or resistance mutations in EGFR. These tests are performed with plasma DNA and have been approved as companion diagnostic test for patients treated with tyrosine kinase inhibitors. ALK is another important target in lung cancer since it leads to treatment of patients who are positive for a rearrangement in ALK identified with tumor tissue. By analogy with EGFR, LB for detection of genomic alterations in ALK (rearrangements or mutations) has been rapidly adopted in the clinic. However, this promising approach has some limitations and has not yet been disseminated as much as the blood test targeting EGFR. In addition to these two therapeutic targets LB can be used for evaluation of the genomic status of other genes of interest of patients with lung cancer (ROS1, RET, NTRK MET, BRAF, HER2, etc.). LB can be performed to evaluate a specific target or for a more or less complex panel of genes. Considering the number of potential targets for clinical trials, techniques of next-generation sequencing of circulating DNA are on the rise. This review will provide an update on the contribution of LB to care of patients with metastatic lung cancer, including the present limits of this approach, and will consider certain perspectives.

Highlights

  • The term “liquid biopsy” (LB) has been created by comparison of the preexisting term tissue biopsy

  • This term should not be used for methods of detection of circulating nucleic acids associated with molecular biology analyses, but only for the detection of circulating tumor cells (CTCs)

  • When an activating mutation is initially detected with plasma DNA in the absence of an associated resistance mutation, a tissue biopsy is recommended to look for an EGFR resistance mutation or other mechanisms of resistance, even if some of the latter can be detected with a LB (Table 2)

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Summary

Introduction

The term “liquid biopsy” (LB) has been created by comparison of the preexisting term tissue biopsy. Should, strictly speaking, be reserved for blood sampling and morphological analysis by microscopy of tumor cells isolated from blood This term should not be used for methods of detection of circulating nucleic acids associated with molecular biology analyses, but only for the detection of circulating tumor cells (CTCs). It is important to distinguish between LB used for clinical research projects and development and LB performed within the framework of healthcare providing immediate benefit to the patient, in particular for those with lung cancer. In this context several therapeutic targets can be detected with circulating nucleic acids (Table 1). Cancers 2017, 9, 154 its theranostic application for patients with non-small cell lung cancer (NSCLC) and will discuss the limits and perspectives of this domain

Mutations in EGFR
Evaluation of the ALK Status with a Liquid Biopsy for Metastatic NSCLC
Mutations in BRAF
Mutations in the RET and HER2 Genes
Evaluation of the MET Status with a Liquid Biopsy
Next-Generation Sequencing Approaches
Liquid Biopsy and Immuno-Oncology
Analysis of Circulating Nucleic Acids
Analysis with Serum
Analysis of the Expression of PD-L1 on Circulating Tumor Cells
Conclusions
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