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Updated: Feb 12, 2026
Establishment and Characterization of Small Bowel Neuroendocrine Tumor Spheroids
Published on: October 14, 2019
Management of functional neuroendocrine tumors of the pancreas
1Department of Medical Sciences, Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden.
Abstract:
Pancreatic neuroendocrine tumors (pNETs) constitute a heterogenous group of malignancies with varying clinical presentation, tumor biology and prognosis. The incidence of pNETs has steadily increased during the last decades with an estimated incidence 2012 of 4.8/100,000. Recent whole genome sequencing of pNETs has demonstrated mutations in the DNA repair genes MUTYH and point mutations and gene fusions in four main pathways from chromatin remodeling, DNA damage repair, activation of mechanistic target of rapamycin (mTOR) signaling and the telomere maintenance. This new information will be the foundation for new therapies in the near future for malignant pNETs. The functioning pNETs constitute about 30-40% of all pNETs displaying nine different clinical syndromes: insulinoma, Zollinger-Ellison, Verner-Morrison, glucagonoma, somatostatinomas, ectopic adrenocorticotropic hormone (ACTH) and parathyroid hormone related peptide (PTH-rP) syndromes. Single patients might also present carcinoid syndrome. The diagnostic work-up include histopathology with the new WHO 2017 Classification, biomarkers (CgA, NSE), radiology and molecular imaging including CT-scan, magnetic resonance imaging (MRI), ultrasound and PET-scan. A cornerstone in the treatment of pNETs is surgery which is rarely curative but can reduce the clinical symptoms by debulking which also include radiofrequency ablation, embolization of liver metastases. Medical treatment includes chemotherapy and the targeted agents such as everolimus, sunitinib and peptide receptor radiotherapy (PRRT). Somatostatin analogs has for the last decades been the main stay for management for clinical symptoms related to functioning pNETs and is often combined with new targeted agents as well as chemotherapy. Long-term management of functioning pNETs need a combination of different procedures, surgery, local ablation, targeted agents and somatostatin analogs. Future therapies might be based on the recent advances in molecular genetics and tumor biology.
Insights
Pancreatic neuroendocrine tumors (pNETs) are increasingly diagnosed. Advances in molecular genetics are paving the way for novel therapies targeting DNA repair and signaling pathways in pNETs.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of malignancies with increasing incidence.
- Recent genomic studies reveal key mutations in DNA repair, chromatin remodeling, mTOR signaling, and telomere maintenance pathways in pNETs.
- Functioning pNETs present with distinct clinical syndromes, requiring comprehensive diagnostic approaches.
Purpose of the Study:
- To summarize the current understanding of pNETs, including their molecular basis, clinical presentations, diagnostic work-up, and treatment strategies.
- To highlight the impact of recent genomic discoveries on the future therapeutic landscape for malignant pNETs.
Main Methods:
- Review of recent whole genome sequencing data for pNETs.
- Analysis of clinical presentations, diagnostic modalities (histopathology, biomarkers, radiology, molecular imaging), and treatment options.
- Synthesis of information on established and emerging therapies.
Main Results:
- Identification of critical mutations in MUTYH, chromatin remodeling, DNA damage repair, mTOR signaling, and telomere maintenance pathways.
- Description of nine distinct clinical syndromes associated with functioning pNETs.
- Overview of diagnostic tools including WHO 2017 Classification, biomarkers (CgA, NSE), and advanced imaging (CT, MRI, PET-scan).
- Summary of treatment modalities: surgery, debulking, radiofrequency ablation, embolization, chemotherapy, targeted agents (everolimus, sunitinib), PRRT, and somatostatin analogs.
Conclusions:
- Genomic insights into pNETs provide a foundation for developing new targeted therapies.
- Effective long-term management of pNETs requires a multimodal approach combining surgery, local ablation, targeted agents, and somatostatin analogs.
- Future therapeutic strategies will be significantly influenced by advances in molecular genetics and tumor biology.
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