Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review
Background: Non-small-cell lung cancer (NSCLC) is recognised as a particularly heterogeneous disease, encompassing a wide spectrum of distinct molecular subtypes. With increased understanding of disease biology and mechanisms of progression, treatment of NSCLC has made remarkable progress in the pas...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2019-09-01
|
Series: | ESMO Open |
Online Access: | https://esmoopen.bmj.com/content/4/5/e000561.full |
id |
doaj-bdb08c5b0362432e8c948447e40c74db |
---|---|
record_format |
Article |
spelling |
doaj-bdb08c5b0362432e8c948447e40c74db2021-04-02T20:45:08ZengElsevierESMO Open2059-70292019-09-014510.1136/esmoopen-2019-000561Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature reviewGeorge Pentheroudakis0Eirini Papadopoulou1George Nasioulas2Anastasia Kougioumtzi3Panagiotis Ntellas4Eleftherios Kampletsas5European Society for Medical Oncology, Lugano, SwitzerlandDiagnostics Laboratory, GeneKor Medical SA, Athens, GreeceDiagnostics Laboratory, GeneKor Medical SA, Athens, GreeceLaboratory of Clinical Chemistry, University of Ioannina School of Medicine, Ioannina, GreeceMedical Oncology, University of Ioannina, Ioannina, GreeceMedical Oncology, University of Ioannina, Ioannina, GreeceBackground: Non-small-cell lung cancer (NSCLC) is recognised as a particularly heterogeneous disease, encompassing a wide spectrum of distinct molecular subtypes. With increased understanding of disease biology and mechanisms of progression, treatment of NSCLC has made remarkable progress in the past two decades. Molecular testing is considered the hallmark for the diagnosis and treatment of NSCLC, with liquid biopsies being more and more often applied in the clinical setting during the recent years. Rearrangement of the ALK gene which results in the generation of fusion oncogenes is a common molecular event in NSCLCs. Among ALK fusion transcripts, EML4-ALK fusion is frequently observed and can be targeted with ALK tyrosine kinase inhibitors (TKI). However, acquired resistance and disease progression in many cases are inevitable.Method: Here, we present the case of a patient with NSCLC treated with TKIs, in which molecular profiling of the tumour was performed with different methods of tissue and plasma testing at each disease progression. A review of the literature was further conducted to offer insights into the resistance mechanisms of ALK-rearranged NSCLC.Conclusions: Based on the results, the EML4-ALK fusion initially detected in tumour tissue was preserved throughout the course of the disease. Two additional ALK mutations were later detected in the tissue and plasma and are likely to have caused resistance to the administered TKIs. Continued research into the mechanisms of acquired resistance is required in order to increase the benefit of the patients treated with targeted ALK TKIs.https://esmoopen.bmj.com/content/4/5/e000561.full |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
George Pentheroudakis Eirini Papadopoulou George Nasioulas Anastasia Kougioumtzi Panagiotis Ntellas Eleftherios Kampletsas |
spellingShingle |
George Pentheroudakis Eirini Papadopoulou George Nasioulas Anastasia Kougioumtzi Panagiotis Ntellas Eleftherios Kampletsas Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review ESMO Open |
author_facet |
George Pentheroudakis Eirini Papadopoulou George Nasioulas Anastasia Kougioumtzi Panagiotis Ntellas Eleftherios Kampletsas |
author_sort |
George Pentheroudakis |
title |
Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review |
title_short |
Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review |
title_full |
Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review |
title_fullStr |
Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review |
title_full_unstemmed |
Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review |
title_sort |
molecular findings reveal possible resistance mechanisms in a patient with alk-rearranged lung cancer: a case report and literature review |
publisher |
Elsevier |
series |
ESMO Open |
issn |
2059-7029 |
publishDate |
2019-09-01 |
description |
Background: Non-small-cell lung cancer (NSCLC) is recognised as a particularly heterogeneous disease, encompassing a wide spectrum of distinct molecular subtypes. With increased understanding of disease biology and mechanisms of progression, treatment of NSCLC has made remarkable progress in the past two decades. Molecular testing is considered the hallmark for the diagnosis and treatment of NSCLC, with liquid biopsies being more and more often applied in the clinical setting during the recent years. Rearrangement of the ALK gene which results in the generation of fusion oncogenes is a common molecular event in NSCLCs. Among ALK fusion transcripts, EML4-ALK fusion is frequently observed and can be targeted with ALK tyrosine kinase inhibitors (TKI). However, acquired resistance and disease progression in many cases are inevitable.Method: Here, we present the case of a patient with NSCLC treated with TKIs, in which molecular profiling of the tumour was performed with different methods of tissue and plasma testing at each disease progression. A review of the literature was further conducted to offer insights into the resistance mechanisms of ALK-rearranged NSCLC.Conclusions: Based on the results, the EML4-ALK fusion initially detected in tumour tissue was preserved throughout the course of the disease. Two additional ALK mutations were later detected in the tissue and plasma and are likely to have caused resistance to the administered TKIs. Continued research into the mechanisms of acquired resistance is required in order to increase the benefit of the patients treated with targeted ALK TKIs. |
url |
https://esmoopen.bmj.com/content/4/5/e000561.full |
work_keys_str_mv |
AT georgepentheroudakis molecularfindingsrevealpossibleresistancemechanismsinapatientwithalkrearrangedlungcanceracasereportandliteraturereview AT eirinipapadopoulou molecularfindingsrevealpossibleresistancemechanismsinapatientwithalkrearrangedlungcanceracasereportandliteraturereview AT georgenasioulas molecularfindingsrevealpossibleresistancemechanismsinapatientwithalkrearrangedlungcanceracasereportandliteraturereview AT anastasiakougioumtzi molecularfindingsrevealpossibleresistancemechanismsinapatientwithalkrearrangedlungcanceracasereportandliteraturereview AT panagiotisntellas molecularfindingsrevealpossibleresistancemechanismsinapatientwithalkrearrangedlungcanceracasereportandliteraturereview AT eleftherioskampletsas molecularfindingsrevealpossibleresistancemechanismsinapatientwithalkrearrangedlungcanceracasereportandliteraturereview |
_version_ |
1721546663468728320 |