ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients

Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression o...

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Main Author: Paul Hofman
Format: Article
Language:English
Published: MDPI AG 2017-08-01
Series:Cancers
Subjects:
ALK
Online Access:https://www.mdpi.com/2072-6694/9/8/106
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spelling doaj-81a4d0ab77fc40fbbd0abb9fcd54333a2020-11-24T21:10:34ZengMDPI AGCancers2072-66942017-08-019810610.3390/cancers9080106cancers9080106ALK Status Assessment with Liquid Biopsies of Lung Cancer PatientsPaul Hofman0Laboratory of Clinical and Experimental Pathology, Côte d’Azur University, FHU OncoAge, 06001 Nice Cedex 01, FrancePatients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation. Therefore, liquid biopsy is an alternative or complementary method to tissue biopsy for the detection of some resistance mutations in EGFR arising during tyrosine kinase inhibitor treatment. Moreover, in some frail patients, or if the tumor lesion is not accessible to a tissue biopsy, a liquid biopsy can also detect some activating mutations in EGFR on initial assessment. Recent studies have evaluated the possibility of also using a liquid biopsy approach to detect an ALK rearrangement and/or the emergence during inhibitor treatment of some resistance mutations in ALK. These assessments can be performed by studying circulating tumor cells by fluorescent in situ hybridization and by immunocytochemistry and/or after the isolation of RNA from plasma samples, free or associated with platelets. Thus, the liquid biopsy may be a complementary or sometimes alternative method for the assessment of the ALK status in certain NSCLC patients, as well as a non-invasive approach for early detection of ALK mutations. In this review, we highlight the current data concerning the role of the liquid biopsy for the ALK status assessment for NSCLC patients, and we compare the different approaches for this evaluation from blood samples.https://www.mdpi.com/2072-6694/9/8/106ALKrearrangementmutationslung cancerliquid biopsycirculating tumor cellsplateletsplasma
collection DOAJ
language English
format Article
sources DOAJ
author Paul Hofman
spellingShingle Paul Hofman
ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients
Cancers
ALK
rearrangement
mutations
lung cancer
liquid biopsy
circulating tumor cells
platelets
plasma
author_facet Paul Hofman
author_sort Paul Hofman
title ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients
title_short ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients
title_full ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients
title_fullStr ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients
title_full_unstemmed ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients
title_sort alk status assessment with liquid biopsies of lung cancer patients
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2017-08-01
description Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation. Therefore, liquid biopsy is an alternative or complementary method to tissue biopsy for the detection of some resistance mutations in EGFR arising during tyrosine kinase inhibitor treatment. Moreover, in some frail patients, or if the tumor lesion is not accessible to a tissue biopsy, a liquid biopsy can also detect some activating mutations in EGFR on initial assessment. Recent studies have evaluated the possibility of also using a liquid biopsy approach to detect an ALK rearrangement and/or the emergence during inhibitor treatment of some resistance mutations in ALK. These assessments can be performed by studying circulating tumor cells by fluorescent in situ hybridization and by immunocytochemistry and/or after the isolation of RNA from plasma samples, free or associated with platelets. Thus, the liquid biopsy may be a complementary or sometimes alternative method for the assessment of the ALK status in certain NSCLC patients, as well as a non-invasive approach for early detection of ALK mutations. In this review, we highlight the current data concerning the role of the liquid biopsy for the ALK status assessment for NSCLC patients, and we compare the different approaches for this evaluation from blood samples.
topic ALK
rearrangement
mutations
lung cancer
liquid biopsy
circulating tumor cells
platelets
plasma
url https://www.mdpi.com/2072-6694/9/8/106
work_keys_str_mv AT paulhofman alkstatusassessmentwithliquidbiopsiesoflungcancerpatients
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