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

Estela Sánchez-Herrero,Atocha Romero,Mariano Provencio

doi:10.1515/almed-2019-0019

Abstract

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. 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. 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.

Highlights

Lung cancer is the most commonly diagnosed cancer along with breast cancer, contributing to more than 8.8 million deaths every year [1]
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

Summary

Introduction

Lung cancer is the most commonly diagnosed cancer along with breast cancer, contributing to more than 8.8 million deaths every year [1]. Different EML4-ALK variants could have distinct sensitivities against the wide variety of ALK-TKI that are nowadays available In this way, as in the case of EGFR mutations, in which tumors with exon deletions are known to be more sensitive to TKIs than tumors harboring other alterations such as exon insertions in exon [25]. The lack of tissue biopsy condemns many patients with rearrangement in ALK to receive chemotherapy instead of ALK-TKIs, with a median overall survival (OS) of ∼12 months instead of ∼50 months from time of diagnosis of metastatic disease as reported by several observational studies using sequential ALK inhibitors [27,28,29,30]. The development of methodologies that allow the non-invasive identification of EML4-ALK translocation, its variants and ALK-TKIs resistance mechanisms remains an unmet clinical need

Liquid biopsy

Future approaches

Findings

Conclusions