Neuroendocrine Tumors: Challenges and Future Perspectives (Second Edition)

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: 5 July 2025 | Viewed by 3039

Special Issue Editors


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Guest Editor
National Center for Drug Research and Evaluation, National Institute of Health (ISS), Rome, Italy
Interests: neuroendocrine tumors; drug development; clinical research; translational research; precision oncology
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Guest Editor
Department of Medical or Surgical Sciences (DIMEC), S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
Interests: neuroendocrine tumors; small-cell lung cancer; immunotherapy; clinical research; precision oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neuroendocrine tumors (NETs) are a family of neoplasms of increasing incidence and prevalence worldwide. Their heterogeneity in terms of biological aggressiveness, variegated site of origin (although they are most commonly gastro-entero-pancreatic in about 60% of the cases and pulmonary in approximately 30% of the cases) and capability to potentially produce hormonally active substances poses unique challenges for clinical management. NETs are characterized by the peculiar and frequent expression on the cell surfaces of somatostatin receptors, which represents the ideal target for therapy (i.e., somatostatin analogues (SSAs) and peptide–receptor radionuclide therapy (PRRT)). Few chemotherapy schemes (such as streptozotocin/5-FU or the association of capecitabine and temozolomide) are currently part of the therapeutic armamentarium. However, regardless of the huge number of clinical trials and many promising new drugs, the only approved targeted agents for advanced progressive NETs are everolimus and sunitinib (the second one only for those of pancreatic origin). Additionally, despite great efforts in the search for innovative biomarkers, only few validated biomarkers are available thus far. Following the success of the first volume of “Neuroendocrine Tumors: Challenges and Future Perspectives” (https://www.mdpi.com/journal/jcm/special_issues/Neuroendocrine_Tumors_Perspectives), a second volume of this Special Issue is announced here with the aim to highlight recent advances in the context of diagnosis, treatment and prediction of prognosis for NETs.

Dr. Anna La Salvia
Dr. Giuseppe Lamberti
Guest Editors

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Keywords

  • neuroendocrine tumors
  • clinical challenges
  • innovative biomarkers
  • novel agents
  • personalized oncology

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Related Special Issue

Published Papers (3 papers)

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Research

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24 pages, 2801 KiB  
Article
Clinicopathological Characteristics of Extrapulmonary Neuroendocrine Carcinomas: Treatment Responses and Survival Outcomes: Single-Center Experience
by Harun Muğlu, Erdem Sünger, Maral Martin Mıldanoğlu, Ebru Engin Delipoyraz, Mehmet Haluk Yücel, Hakan Özçelik, Jamshid Hamdard, Özgür Açıkgöz, Ömer Fatih Ölmez, Özcan Yıldız and Ahmet Bilici
J. Clin. Med. 2025, 14(7), 2264; https://doi.org/10.3390/jcm14072264 - 26 Mar 2025
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Abstract
 Background/Objectives: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of [...] Read more.
 Background/Objectives: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of EP-NEC patients, their treatment responses, and survival outcomes. Methods: This retrospective observational study included 29 EP-NEC patients diagnosed and followed between 2015 and 2024. Clinical and demographic data, tumor localization, disease stage, administered treatments, and survival outcomes were analyzed. Kaplan–Meier survival analysis was used to assess OS and PFS, with subgroup comparisons performed via the log-rank test. Results: The most common primary tumor sites were the pancreas (21%), prostate (17%), and cervix (14%). At diagnosis, 55.2% of patients had metastatic disease. First-line platinum-based chemotherapy achieved an objective response rate of 82.1%, with a median PFS of 8.16 months and a median OS of 14.16 months. Surgical intervention significantly improved survival (p = 0.020), while a high Ki-67 proliferation index (>80%) was associated with worse PFS (p = 0.032). Other factors, including smoking status and liver-directed therapies, had no significant impact on survival. Conclusions: EP-NECs present with a poor prognosis despite platinum-based chemotherapy achieving high response rates. Surgical resection improves survival outcomes, whereas high Ki-67 expression is associated with a worse prognosis. These findings highlight the need for further research into novel therapeutic strategies for EP-NECs. Full article
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Review

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12 pages, 531 KiB  
Review
Gastroenteropancreatic Neuroendocrine Neoplasms and Celiac Disease: Rare or Neglected Association?
by Luca Pes, Anna La Salvia, Giovanni Mario Pes, Maria Pina Dore and Giuseppe Fanciulli
J. Clin. Med. 2025, 14(3), 780; https://doi.org/10.3390/jcm14030780 - 25 Jan 2025
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Abstract
Background: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors originating from neuroendocrine cells in the gastroenteropancreatic system. They are increasingly recognized as being potentially associated with chronic intestinal inflammatory conditions, namely Crohn’s disease and ulcerative colitis. Celiac disease (CD) is an immune-mediated chronic gastrointestinal [...] Read more.
Background: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors originating from neuroendocrine cells in the gastroenteropancreatic system. They are increasingly recognized as being potentially associated with chronic intestinal inflammatory conditions, namely Crohn’s disease and ulcerative colitis. Celiac disease (CD) is an immune-mediated chronic gastrointestinal inflammation triggered by gluten in genetically predisposed individuals. This study aimed to explore the relationship between GEP-NENs and CD, providing a detailed review of the existing literature and addressing the (possible) gaps in current knowledge. Methods: We conducted an extensive search of international databases using relevant keywords, with the last update on 1 November 2024. A total of 19 studies, published between 1983 and 2024, were included: two prospective studies, five retrospective studies, and 12 case reports. Results: Overall, we included 107 GEP-NENs in our analysis. Among the 94 GEP-NENs identified in prospective and retrospective studies, the small intestine was the most common site (88.3%). The small intestine was also the most frequently reported site in the case report series (46.2%), accounting for 13 GEP-NENs in 12 patients with CD. Conclusions: Although most studies on the association between CD and GEP-NENs are heterogeneous, and while some lack crucial data, emerging evidence suggests that screening GEP-NEN patients for CD could offer valuable insights. Testing for the presence of CD might reveal whether the observed association is more than coincidental and possibly pave the way for exploring and understanding the role of chronic inflammation in the tumorigenesis of GEP-NENs in CD. Full article
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Other

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18 pages, 6278 KiB  
Case Report
Pancreatic Neuroendocrine Tumor: The Case Report of a Patient with Germline FANCD2 Mutation and Tumor Analysis Using Single-Cell RNA Sequencing
by Ekaterina Avsievich, Diana Salimgereeva, Alesia Maluchenko, Zoia Antysheva, Mark Voloshin, Ilia Feidorov, Olga Glazova, Ivan Abramov, Denis Maksimov, Samira Kaziakhmedova, Natalia Bodunova, Nikolay Karnaukhov, Pavel Volchkov and Julia Krupinova
J. Clin. Med. 2024, 13(24), 7621; https://doi.org/10.3390/jcm13247621 - 14 Dec 2024
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Abstract
Background: Neuroendocrine neoplasms are a rare and heterogeneous group of neoplasms. Small-sized (≤2 cm) pancreatic neuroendocrine tumors (PanNETs) are of particular interest as they are often associated with aggressive behavior, with no specific prognostic or progression markers. Methods: This article describes a clinical [...] Read more.
Background: Neuroendocrine neoplasms are a rare and heterogeneous group of neoplasms. Small-sized (≤2 cm) pancreatic neuroendocrine tumors (PanNETs) are of particular interest as they are often associated with aggressive behavior, with no specific prognostic or progression markers. Methods: This article describes a clinical case characterized by a progressive growth of nonfunctional PanNET requiring surgical treatment in a patient with a germline FANCD2 mutation, previously not reported in PanNETs. The patient underwent whole exome sequencing and single-cell RNA sequencing. Results: The patient underwent surgical treatment. We confirmed the presence of the germline mutation FANCD2 and also detected the germline mutation WNT10A. The cellular composition of the PanNET was analyzed using single-cell sequencing, and the main cell clusters were identified. We analyzed the tumor genomics, and used the data to define the effect the germline FANCD2 mutation had. Conclusions: Analysis of the mutational status of patients with PanNET may provide additional data that may influence treatment tactics, refine the plan for monitoring such patients, and provide more information about the pathogenesis of PanNET. PanNET research using scRNA-seq data may help in predicting the effect of therapy on neuroendocrine cells with FANCD2 mutations. Full article
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