Clinical utility of liquid biopsy for the diagnosis and monitoring of EML4-ALK NSCLC patients

Adv Lab Med. 2020 Mar 18;1(1):20190019. doi: 10.1515/almed-2019-0019. eCollection 2020 Mar.
[Article in English, Spanish]

Abstract

Background: Genomic rearrangement in anaplastic lymphoma kinase (ALK) gene occurs in 3-7% of patients with non-small-cell lung cancer (NSCLC). The detection of this alteration is crucial as ALK positive NSCLC patients benefit from ALK inhibitors, which improve both the patient's quality of life and overall survival (OS) compared to traditional chemotherapy.

Content: In routine clinical practice, ALK rearrangements are detected using tissue biopsy. Nevertheless, the availability of tumor tissue is compromised in NSCLC patients due to surgical complications or difficult access to the cancer lesion. In addition, DNA quality and heterogeneity may impair tumor biopsies testing. These limitations can be overcome by liquid biopsy, which refers to non-invasive approaches for tumor molecular profiling. In this paper we review currently available technology for non-invasive ALK testing, in NSCLC patients, based on the analysis of circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), circulating tumor cells (CTCs), tumor-educated platelets (TEPs) and extracellular vesicles (EVs) such as exosomes.

Summary and outlook: Non-invasive tumor molecular profiling is crucial to improve outcomes and quality of life of NSCLC patients whose tumors harbor a translocation involving ALK locus.

Keywords: anaplastic lymphoma kinase; circulating free DNA; exosomes; liquid biopsy; non-small-cell lung cancer; tyrosine kinase inhibitors.

Publication types

  • Review

Grants and funding

This study was supported by the Carlos III Institute of Health, the Spanish Ministry of Science and Innovation and the European Regional Development Fund (grant number: PIE17/01977). ES was financed by the Consejería de Educación, Juventud y Deporte of Comunidad de Madrid and by the Fondo Social Europeo (Programa Operativo de Empleo Juvenil, and Iniciativa de Empleo Juvenil, PEJ-2017-AI/SAL-6478).