Case Report: A novel ELMOD3-ALK and EML4-ALK double-fusion responses to neoadjuvant alectinib in a lung adenocarcinoma patient
BackgroundAnaplastic lymphoma kinase (ALK) rearrangements account for approximately 3%–5% of non-small cell lung cancer (NSCLC), and the echinoderm microtubule-associated protein-like 4 gene (EML4) and ALK fusion (EML4-ALK) is the most common ALK rearrangement in NSCLC patients. However, double-ALK...
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Frontiers Media S.A.
2025-04-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1515826/full |
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| author | Kaili Huang Kaili Huang Wen Li Wen Li Yinyin Xue Yinyin Xue Lei Peng Lei Peng Qiang Wu Qiang Wu Qinghua Zhou Qinghua Zhou |
| author_facet | Kaili Huang Kaili Huang Wen Li Wen Li Yinyin Xue Yinyin Xue Lei Peng Lei Peng Qiang Wu Qiang Wu Qinghua Zhou Qinghua Zhou |
| author_sort | Kaili Huang |
| collection | DOAJ |
| description | BackgroundAnaplastic lymphoma kinase (ALK) rearrangements account for approximately 3%–5% of non-small cell lung cancer (NSCLC), and the echinoderm microtubule-associated protein-like 4 gene (EML4) and ALK fusion (EML4-ALK) is the most common ALK rearrangement in NSCLC patients. However, double-ALK fusion is extremely rare in clinical practice. Herein, we first report a lung adenocarcinoma patient with the coexistence of a novel subfamily 3 of ELMOD (ELMOD3)-ALK, EML4-ALK double fusion that is sensitive to alectinib target therapy.Materials and methodsHematoxylin–eosin (H&E) staining, immunohistochemistry (IHC), and next-generation sequencing (NGS) were performed on biopsy samples.ResultsThe IHC analysis confirmed positive expression of ALK protein. NGS revealed a novel ELMOD3-ALK and EML4-ALK double fusion. The patient was sensitive to alectinib as neoadjuvant therapy and achieved a major pathological response (MPR), which was confirmed by the postoperative pathology diagnosis. To date, the patients’ disease-free survival (DFS) has exceeded 4 years without any significant symptoms of toxicity.ConclusionThis is the first report of one lung adenocarcinoma patient with a novel ELMOD3-ALK, EML4-ALK double-ALK fusion. This double-ALK fusion variant is sensitive to alectinib, suggesting patients with an ELMOD3-ALK, EML4-ALK double-ALK fusion could achieve clinical survival benefit from alectinib. |
| format | Article |
| id | doaj-art-d0eeb01352c74cdc9a73de42599da6ff |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-d0eeb01352c74cdc9a73de42599da6ff2025-08-20T02:12:10ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15158261515826Case Report: A novel ELMOD3-ALK and EML4-ALK double-fusion responses to neoadjuvant alectinib in a lung adenocarcinoma patientKaili Huang0Kaili Huang1Wen Li2Wen Li3Yinyin Xue4Yinyin Xue5Lei Peng6Lei Peng7Qiang Wu8Qiang Wu9Qinghua Zhou10Qinghua Zhou11Lung Cancer Center and Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLung Cancer Center and Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLung Cancer Center and Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLung Cancer Center and Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLung Cancer Center and Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLung Cancer Center and Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaBackgroundAnaplastic lymphoma kinase (ALK) rearrangements account for approximately 3%–5% of non-small cell lung cancer (NSCLC), and the echinoderm microtubule-associated protein-like 4 gene (EML4) and ALK fusion (EML4-ALK) is the most common ALK rearrangement in NSCLC patients. However, double-ALK fusion is extremely rare in clinical practice. Herein, we first report a lung adenocarcinoma patient with the coexistence of a novel subfamily 3 of ELMOD (ELMOD3)-ALK, EML4-ALK double fusion that is sensitive to alectinib target therapy.Materials and methodsHematoxylin–eosin (H&E) staining, immunohistochemistry (IHC), and next-generation sequencing (NGS) were performed on biopsy samples.ResultsThe IHC analysis confirmed positive expression of ALK protein. NGS revealed a novel ELMOD3-ALK and EML4-ALK double fusion. The patient was sensitive to alectinib as neoadjuvant therapy and achieved a major pathological response (MPR), which was confirmed by the postoperative pathology diagnosis. To date, the patients’ disease-free survival (DFS) has exceeded 4 years without any significant symptoms of toxicity.ConclusionThis is the first report of one lung adenocarcinoma patient with a novel ELMOD3-ALK, EML4-ALK double-ALK fusion. This double-ALK fusion variant is sensitive to alectinib, suggesting patients with an ELMOD3-ALK, EML4-ALK double-ALK fusion could achieve clinical survival benefit from alectinib.https://www.frontiersin.org/articles/10.3389/fphar.2025.1515826/fulllung adenocarcinomaALKELMOD3double fusionneoadjuvant alectinib |
| spellingShingle | Kaili Huang Kaili Huang Wen Li Wen Li Yinyin Xue Yinyin Xue Lei Peng Lei Peng Qiang Wu Qiang Wu Qinghua Zhou Qinghua Zhou Case Report: A novel ELMOD3-ALK and EML4-ALK double-fusion responses to neoadjuvant alectinib in a lung adenocarcinoma patient Frontiers in Pharmacology lung adenocarcinoma ALK ELMOD3 double fusion neoadjuvant alectinib |
| title | Case Report: A novel ELMOD3-ALK and EML4-ALK double-fusion responses to neoadjuvant alectinib in a lung adenocarcinoma patient |
| title_full | Case Report: A novel ELMOD3-ALK and EML4-ALK double-fusion responses to neoadjuvant alectinib in a lung adenocarcinoma patient |
| title_fullStr | Case Report: A novel ELMOD3-ALK and EML4-ALK double-fusion responses to neoadjuvant alectinib in a lung adenocarcinoma patient |
| title_full_unstemmed | Case Report: A novel ELMOD3-ALK and EML4-ALK double-fusion responses to neoadjuvant alectinib in a lung adenocarcinoma patient |
| title_short | Case Report: A novel ELMOD3-ALK and EML4-ALK double-fusion responses to neoadjuvant alectinib in a lung adenocarcinoma patient |
| title_sort | case report a novel elmod3 alk and eml4 alk double fusion responses to neoadjuvant alectinib in a lung adenocarcinoma patient |
| topic | lung adenocarcinoma ALK ELMOD3 double fusion neoadjuvant alectinib |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1515826/full |
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