Future Perspectives in Detecting EGFR and ALK Gene Alterations in Liquid Biopsies of Patients with NSCLC.

Filomena Adega,Daniela Ferreira,Juliana Miranda,Raquel Chaves,Paula Martins-Lopes

doi:10.3390/ijms22083815

Abstract

Non-small-cell lung cancer (NSCLC) is a major cause of death worldwide. Alterations in such genes as EGFR and ALK are considered important biomarkers in NSCLC due to the existence of targeted therapies with specific tyrosine kinase inhibitors (TKIs). However, specific resistance-related mutations can occur during TKI treatment, which often result in therapy inefficacy. Liquid biopsies arise as a reliable tool for the early detection of these types of alterations, allowing a non-invasive follow-up of the patients. Furthermore, they can be essential for cancer screening, initial diagnosis and to check surgery success. Despite the great advantages of liquid biopsies in NSCLC and the high input that next-generation sequencing (NGS) approaches can provide in this field, its use in oncology is still limited. With improvement of assay sensitivity and the establishment of clinical guidelines for liquid biopsy analysis, it is expected that they will be used in routine procedures. This review focuses on the usefulness of liquid biopsies of NSCLC patients as a means to detect alterations in EGFR and ALK genes and in disease management, highlighting the impact of NGS methods.

Highlights

The EGFR mutation p.T790M occurs in more than 50% of Non-small-cell lung cancer (NSCLC) patients treated with the first- and second-generation EGFR tyrosine kinase inhibitors (TKIs), resulting in therapy inefficacy [7,8,9]
The resistance observed in NSCLC patients treated with these EGFR TKIs resulted in the development of the second-generation of TKIs, such as afatinib, canertinib, dacomitinib, neratinib and pelitinib
The AURA trials demonstrated the clinical potential of ctDNA testing for EGFR mutation p.T790M detection in plasma from NSCLC when the efficacy, dose and safety of osimertinib were evaluated

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. TKI treatments [5,6] These biomarkers are scrutinized in the initial diagnosis (usually by PCR and Sanger sequencing methods) to define the therapy according to the molecular profile, a high number of patients acquire resistance during treatment. Liquid biopsies emerged as a reliable approach to overcome these issues, still requiring further research considering sensitivity They are defined as the use of patient’s body fluids (e.g., blood, urine, saliva and pleural effusion) to determine tumor-specific alterations [11]. We present an update on the perspective of detecting EGFR and ALK gene alterations in liquid biopsies of patients with NSCLC, focusing on new methods that have emerged in the past few years and on the impact of NGS

Alterations in EGFR and ALK Genes as Predictive Biomarkers in NSCLC

Mutations in EGFR as Predictive Biomarkers and EGFR TKIs in NSCLC

Alterations in ALK as Predictive Biomarkers and ALK TKIs in NSCLC

State of the Art on the Analysis of EGFR and ALK Mutations in Liquid

Method

Findings

Conclusions