Case report: Two novel intergenic region-ALK fusions in non-small-cell lung cancer resistant to alectinib: A report of two cases

BACKGROUND: The anaplastic lymphoma kinase (ALK) mutation, also known as the diamond mutation in non–small-cell lung cancer (NSCLC), has been treated with tremendous success since it was first reported in 2007. Alectinib, a second generation ALK-Tyrosine kinase inhibitor (TKI), has been reported to...

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Autores principales: Liao, Shan, Sun, Huiying, Wu, Jianhua, Lu, Hao, Fang, Yisheng, Wang, Yuanyuan, Liao, Wangjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356229/
https://www.ncbi.nlm.nih.gov/pubmed/35941871
http://dx.doi.org/10.3389/fonc.2022.916315
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author Liao, Shan
Sun, Huiying
Wu, Jianhua
Lu, Hao
Fang, Yisheng
Wang, Yuanyuan
Liao, Wangjun
author_facet Liao, Shan
Sun, Huiying
Wu, Jianhua
Lu, Hao
Fang, Yisheng
Wang, Yuanyuan
Liao, Wangjun
author_sort Liao, Shan
collection PubMed
description BACKGROUND: The anaplastic lymphoma kinase (ALK) mutation, also known as the diamond mutation in non–small-cell lung cancer (NSCLC), has been treated with tremendous success since it was first reported in 2007. Alectinib, a second generation ALK-Tyrosine kinase inhibitor (TKI), has been reported to have significantly longer progression- free survival (PFS) than first generation ALK inhibitors in untreated ALK positive NSCLC. However, the clinical efficacy of ALK-TKIs on rare ALK fusions remains unclear. In recent years, with the popularity of next-generation sequencing (NGS) technology, an increasing number of novel ALK fusion partners have been reported, but the responses are heterogeneous among different ALK fusions. Considering the inconsistent reactions, the clinical efficacy of ALK-TKIs in rare ALK gene fusions remains to be evaluated in more cases. METHODS: To seek for individualized therapy, the tumor tissues acquired during biopsy were sent for genomic testing by NGS based on a 139-gene panel and a 425-gene panel in a centralized clinical testing center (GENESEEQ Technology Inc, Nanjing, China). See Supplementary Material for more details about the methods for DNA-based NGS, RNA-based NGS. RESULTS: We present two cases of patients with lung adenocarcinoma harboring two novel Intergenic Region (IGR)-ALK rearrangements detected by DNA sequencing, which had limited clinical response to ALK-TKIs but showed sensitivity to chemotherapy combined with bevacizumab therapy in patient 2, with a PFS of over 1 year up till the last follow‐up assessment. CONCLUSIONS: In summary, our cases emphasize the need for comprehensive molecular analysis of different ALK fusion partners at the DNA level to formulate accurate treatment strategies and provide a certain therapeutic reference for these two types of novel IGR-ALK fusions.
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spelling pubmed-93562292022-08-07 Case report: Two novel intergenic region-ALK fusions in non-small-cell lung cancer resistant to alectinib: A report of two cases Liao, Shan Sun, Huiying Wu, Jianhua Lu, Hao Fang, Yisheng Wang, Yuanyuan Liao, Wangjun Front Oncol Oncology BACKGROUND: The anaplastic lymphoma kinase (ALK) mutation, also known as the diamond mutation in non–small-cell lung cancer (NSCLC), has been treated with tremendous success since it was first reported in 2007. Alectinib, a second generation ALK-Tyrosine kinase inhibitor (TKI), has been reported to have significantly longer progression- free survival (PFS) than first generation ALK inhibitors in untreated ALK positive NSCLC. However, the clinical efficacy of ALK-TKIs on rare ALK fusions remains unclear. In recent years, with the popularity of next-generation sequencing (NGS) technology, an increasing number of novel ALK fusion partners have been reported, but the responses are heterogeneous among different ALK fusions. Considering the inconsistent reactions, the clinical efficacy of ALK-TKIs in rare ALK gene fusions remains to be evaluated in more cases. METHODS: To seek for individualized therapy, the tumor tissues acquired during biopsy were sent for genomic testing by NGS based on a 139-gene panel and a 425-gene panel in a centralized clinical testing center (GENESEEQ Technology Inc, Nanjing, China). See Supplementary Material for more details about the methods for DNA-based NGS, RNA-based NGS. RESULTS: We present two cases of patients with lung adenocarcinoma harboring two novel Intergenic Region (IGR)-ALK rearrangements detected by DNA sequencing, which had limited clinical response to ALK-TKIs but showed sensitivity to chemotherapy combined with bevacizumab therapy in patient 2, with a PFS of over 1 year up till the last follow‐up assessment. CONCLUSIONS: In summary, our cases emphasize the need for comprehensive molecular analysis of different ALK fusion partners at the DNA level to formulate accurate treatment strategies and provide a certain therapeutic reference for these two types of novel IGR-ALK fusions. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9356229/ /pubmed/35941871 http://dx.doi.org/10.3389/fonc.2022.916315 Text en Copyright © 2022 Liao, Sun, Wu, Lu, Fang, Wang and Liao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Liao, Shan
Sun, Huiying
Wu, Jianhua
Lu, Hao
Fang, Yisheng
Wang, Yuanyuan
Liao, Wangjun
Case report: Two novel intergenic region-ALK fusions in non-small-cell lung cancer resistant to alectinib: A report of two cases
title Case report: Two novel intergenic region-ALK fusions in non-small-cell lung cancer resistant to alectinib: A report of two cases
title_full Case report: Two novel intergenic region-ALK fusions in non-small-cell lung cancer resistant to alectinib: A report of two cases
title_fullStr Case report: Two novel intergenic region-ALK fusions in non-small-cell lung cancer resistant to alectinib: A report of two cases
title_full_unstemmed Case report: Two novel intergenic region-ALK fusions in non-small-cell lung cancer resistant to alectinib: A report of two cases
title_short Case report: Two novel intergenic region-ALK fusions in non-small-cell lung cancer resistant to alectinib: A report of two cases
title_sort case report: two novel intergenic region-alk fusions in non-small-cell lung cancer resistant to alectinib: a report of two cases
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356229/
https://www.ncbi.nlm.nih.gov/pubmed/35941871
http://dx.doi.org/10.3389/fonc.2022.916315
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