ArticleEndocrine-related cancer2021
Targeting EML4-ALK gene fusion variant 3 in thyroid cancer.
Article in Endocrine-related cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Radioiodine-Refractory Differentiated Thyroid Cancer: Definition, Molecular Mechanisms, and Advances in Precision Therapy.Cancer innovation · 2026Review
- Current Research in Polypharmacology for Cancer Treatment Using Dual-Target Histone Deacetylase Inhibitors.International journal of molecular sciences · 2026Review
- The Occurrence of Gene Fusions in Thyroid Lesions and the Relation With Chronic Lymphocytic Thyroiditis.Pathology international · 2026Article
- Case Report: Lorlatinib for the treatment ofFrontiers in oncology · 2026Article
- FAM172A promotes epithelial ovarian cancer progression and induces platinum resistance via the PI3K/AKT pathway.Scientific reports · 2025Article
- Recurrent Poorly Differentiated Thyroid Cancer Successfully Treated With Radiation and Immunotherapy.JCEM case reports · 2025Article
- Novel ALK gene mutation in inflammatory myofibroblastic tumor of the thyroid: a case report.Frontiers in oncology · 2025Article
- Metastatic Non-Myofibroblastic Sarcoma Harbouring EML4-ALK Fusion-Dramatic Response to ALK Tyrosine Kinase Inhibitors and Development of Resistance Mutations.Cancer reports (Hoboken, N.J.) · 2024Article
- Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy.Frontiers in immunology · 2024Review
- Efficacy and safety of compassionate use for rare diseases: a scoping review from 1991 to 2022.Orphanet journal of rare diseases · 2023Article
- Molecular Profiling of 50 734 Bethesda III-VI Thyroid Nodules by ThyroSeq v3: Implications for Personalized Management.The Journal of clinical endocrinology and metabolism · 2023Article
- Inhibition of ALK-Signaling Overcomes STRN-ALK-Induced Downregulation of the Sodium Iodine Symporter and Restores Radioiodine Uptake in Thyroid Cells.Thyroid : official journal of the American Thyroid Association · 2023Article
- Kinase inhibitors in thyroid cancers.Endocrine oncology (Bristol, England) · 2023Review
- Case Report ofThyroid : official journal of the American Thyroid Association · 2022Article
- EML4-ALK fusion gene in non-small cell lung cancer.Oncology letters · 2022Review
- Anaplastic lymphoma kinase inhibitors and their effect on the kidney.Clinical kidney journal · 2022Review
- State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer.International journal of molecular sciences · 2022Review
- Remarkable response to alectinib for metastatic papillary thyroid cancer with STRN-ALK fusion: A case report.Frontiers in oncology · 2022Article
- Novel Inhibitor-Based Therapies for Thyroid Cancer-An Update.International journal of molecular sciences · 2021Review
- Issues with the targeted therapy of non‑small cell lung cancer with thyroid metastases: A case report.Medicine internationalArticle
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Finding targetable gene fusions can expand the limited treatment options in radioactive iodine-refractory (RAI-r) thyroid cancer. To that end, we established a novel cell line 'JVE404' derived from an advanced RAI-r papillary thyroid cancer (PTC) patient, harboring an EML4-ALK gene fusion variant 3 (v3). Different EML4-ALK gene fusions can have different clinical repercussions. JVE404 cells were evaluated for cell viability and cell signaling in response to ALK inhibitors crizotinib, ceritinib and lorlatinib, in parallel to the patient's treatment. He received, after first-line lenvatinib, crizotinib (Drug Rediscovery Protocol (DRUP) trial), and lorlatinib (compassionate use). In vitro treatment with crizotinib or ceritinib decreased viability in JVE404, but most potently and significantly only with lorlatinib. Western blot analysis showed a near total decrease of 99% and 89%, respectively, in pALK and pERK expression levels in JVE404 cells with lorlatinib, in contrast to remaining signal intensities of a half and a third of control, respectively, with crizotinib. The patient had a 6-month lasting stable disease on crizotinib, but progressive disease occurred, including the finding of cerebral metastases, at 8 months. With lorlatinib, partial response, including clinical cerebral activity, was already achieved at 11 weeks' use and ongoing partial response at 7 months. To our best knowledge, this is the first reported case describing a patient-specific targeted treatment with lorlatinib based on an EML4-ALK gene fusion v3 in a thyroid cancer patient, and own cancer cell line. Tumor-agnostic targeted therapy may provide valuable treatment options in personalized medicine.
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