ArticleCellular oncology (Dordrecht, Netherlands)2022
Novel preclinical gastroenteropancreatic neuroendocrine neoplasia models demonstrate the feasibility of mutation-based targeted therapy.
Article in Cellular oncology (Dordrecht, Netherlands), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 19 citations in OpenAlex.
- Establishment of patient-derived xenografts for neuroendocrine tumors in the avian embryo model.Endocrine-related cancer · 2026Article
- White paper on best practices for translational research in neuroendocrine neoplasms.Journal of neuroendocrinology · 2025Article
- Improving neuroendocrine tumor treatments with mathematical modeling: lessons from other endocrine cancers.Endocrine oncology (Bristol, England) · 2025Review
- Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?Endocrine pathology · 2024Review
- Telomere-related DNA damage response pathways in cancer therapy: prospective targets.Frontiers in pharmacology · 2024Review
- NET Models Meeting 2024 white paper: the current state of neuroendocrine tumour research models and our future aspirations.Endocrine oncology (Bristol, England) · 2024Review
- Models in Pancreatic Neuroendocrine Neoplasms: Current Perspectives and Future Directions.Cancers · 2023Review
- Preclinical Models of Neuroendocrine Neoplasia.Cancers · 2022Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) form a rare and remarkably heterogeneous group of tumors. Therefore, establishing personalized therapies is eminently challenging. To achieve progress in preclinical drug development, there is an urgent need for relevant tumor models.
methodsWe successfully established three gastroenteropancreatic neuroendocrine tumor (GEP-NET) cell lines (NT-18P, NT-18LM, NT-36) and two gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) cell lines (NT-32 and NT-38). We performed a comprehensive characterization of morphology, NET differentiation, proliferation and intracellular signaling pathways of these five cell lines and, in addition, of the NT-3 GEP-NET cell line. Additionally, we conducted panel sequencing to identify genomic alterations suitable for mutation-based targeted therapy.
resultsWe found that the GEP-NEN cell lines exhibit a stable neuroendocrine phenotype. Functional kinome profiling revealed a higher activity of serine/threonine kinases (STK) as well as protein tyrosine kinases (PTK) in the GEP-NET cell lines NT-3 and NT-18LM compared to the GEP-NEC cell lines NT-32 and NT-38. Panel sequencing revealed a mutation in Death Domain Associated Protein (DAXX), sensitizing NT-18LM to the Ataxia telangiectasia and Rad3 related (ATR) inhibitor Berzosertib, and a mutation in AT-Rich Interaction Domain 1A (ARID1A), sensitizing NT-38 to the Aurora kinase A inhibitor Alisertib. Small interfering RNA-mediated knock down of DAXX in the DAXX wild type cell line NT-3 sensitized these cells to Berzosertib.
conclusionsThe newly established GEP-NET and GEP-NEC cell lines represent comprehensive preclinical in vitro models suitable to decipher GEP-NEN biology and pathogenesis. Additionally, we present the first results of a GEP-NEN-specific mutation-based targeted therapy. These findings open up new potentialities for personalized therapies in GEP-NEN.
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