Updates in Neuroendocrine Neoplasms

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 15 April 2025 | Viewed by 2497

Special Issue Editor


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Guest Editor
Department of GI Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Interests: neuroendocrine tumors; neuroendocrine carcinomas; peptide receptor radionuclide therapy; targeted therapy

Special Issue Information

Dear Colleagues,

The treatment landscape of neuroendocrine neoplasms continues to evolve with novel targeted drugs, radioligands, and immune therapies. This Special Issue aims to explore the role of chemotherapy, liver-directed treatment, targeted therapy, immune therapy, and peptide receptor radionuclide therapy, as well as the interaction between these treatments. The implications of new molecular findings will also be explored in this Special Issue.

Dr. Jonathan Strosberg
Guest Editor

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Keywords

  • neuroendocrine tumors
  • neuroendocrine neoplasms
  • neuroendocrine carcinomas
  • therapy
  • germline mutations
  • somatic mutations

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Published Papers (3 papers)

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20 pages, 2673 KiB  
Article
Immune Cell Molecular Pharmacodynamics of Lanreotide in Relation to Treatment Response in Patients with Gastroenteropancreatic Neuroendocrine Tumors
by Sabah Alaklabi, Orla Maguire, Harsha Pattnaik, Yali Zhang, Jacky Chow, Jianmin Wang, Hans Minderman and Renuka Iyer
Cancers 2024, 16(17), 3104; https://doi.org/10.3390/cancers16173104 - 7 Sep 2024
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Abstract
The CLARINET trial led to the approval of lanreotide for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (NETs). It is hypothesized that lanreotide regulates proliferation, hormone synthesis, and other cellular functions via binding to somatostatin receptors (SSTR1–5) present in NETs. However, our [...] Read more.
The CLARINET trial led to the approval of lanreotide for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (NETs). It is hypothesized that lanreotide regulates proliferation, hormone synthesis, and other cellular functions via binding to somatostatin receptors (SSTR1–5) present in NETs. However, our knowledge of how lanreotide affects the immune system is limited. In vitro studies have investigated functional immune response parameters with lanreotide treatment in healthy donor T cell subsets, encompassing the breadth of SSTR expression, apoptosis induction, cytokine production, and activity of transcription factor signaling pathways. In our study, we characterized in vitro immune mechanisms in healthy donor T cells in response to lanreotide. We also studied the in vivo effects by looking at differential gene expression pre- and post-lanreotide therapy in patients with NET. Immune-focused gene and protein expression profiling was performed on peripheral blood samples from 17 NET patients and correlated with clinical response. In vivo, lanreotide therapy showed reduced effects on wnt, T cell receptor (TCR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling in CD8+ T cells in responders compared to non-responders. Compared to non-responders, responders showed reduced effects on cytokine and chemokine signaling but greater effects on ubiquitination and proteasome degradation genes. Our results suggest significant lanreotide pharmacodynamic effects on immune function in vivo, which correlate with responses in NET patients. This is not evident from experimental in vitro settings. Full article
(This article belongs to the Special Issue Updates in Neuroendocrine Neoplasms)
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8 pages, 1496 KiB  
Article
Safety and Efficacy of Peptide Receptor Radionuclide Therapy (PRRT) Following Bland Embolization for Metastatic Neuroendocrine Tumors
by Adam Alayli, Hoang Ngo, Dhiraj Sikaria, Altan Ahmed, Elias Salloum, Jonathan R. Strosberg, Taymeyah E. Al-Toubah, Bela Kis, Mintallah Haider and Ghassan El-Haddad
Cancers 2024, 16(15), 2703; https://doi.org/10.3390/cancers16152703 - 30 Jul 2024
Cited by 1 | Viewed by 783
Abstract
Rationale: Evaluating the long-term safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumors (mNETs) who have undergone prior bland hepatic transarterial embolization (TAE). Methods: Retrospective review of mNET patients who received PRRT with 177Lu-DOTATATE [...] Read more.
Rationale: Evaluating the long-term safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumors (mNETs) who have undergone prior bland hepatic transarterial embolization (TAE). Methods: Retrospective review of mNET patients who received PRRT with 177Lu-DOTATATE between 4/2018 and 02/2022 with and without prior TAE. The most recent clinical, imaging, and laboratory findings, including hepatic Common Terminology Criteria for Adverse Events v5.0, were compared to pre-PRRT. Results: 171 patients (95 M, 76 F, median age = 66) with mNET of different primary sites (9 foregut, 100 midgut, 9 hindgut, 44 pancreas, 9 unknown) received at least 1 cycle of PRRT with at least 6 months of follow-up, 110 of whom were embolization-naïve and 61 who had prior TAE. The median follow up was 22 months (range: 6–43). Patients with prior TAE had higher liver tumor burden on average than patients without prior TAE; however, the difference was not statistically significant (p = 0.06). There was no significant difference in the rates of G3 or G4 hepatotoxicity (p = 0.548 and p = 0.999, respectively) in patients who underwent prior TAE and those who were TAE-naïve. The hepatic progression-free survival was 22.9 months in TAE-naïve patients and 25.7, 20.2, and 12.8 months in patients with 1, 2, and 3 prior TAE treatments, respectively. Conclusion: Peptide receptor radionuclide therapy following transarterial bland embolization for mNET is safe and effective. Full article
(This article belongs to the Special Issue Updates in Neuroendocrine Neoplasms)
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12 pages, 550 KiB  
Systematic Review
The Role of Liquid Biopsy in Gastroenteropancreatic Neuroendocrine Neoplasms
by Catarina Almeida, Lorenzo Gervaso, Gianmaria Frigè, Francesca Spada, Lavinia Benini, Chiara Alessandra Cella, Luca Mazzarella and Nicola Fazio
Cancers 2024, 16(19), 3349; https://doi.org/10.3390/cancers16193349 - 30 Sep 2024
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Abstract
Neuroendocrine neoplasms incidence has been increasing, arising the need for precise and early diagnostic tools. Liquid biopsy (LB) offers a less invasive alternative to tissue biopsy, providing real-time molecular information from circulating tumour components in body fluids. The aim of this review is [...] Read more.
Neuroendocrine neoplasms incidence has been increasing, arising the need for precise and early diagnostic tools. Liquid biopsy (LB) offers a less invasive alternative to tissue biopsy, providing real-time molecular information from circulating tumour components in body fluids. The aim of this review is to analyse the current evidence concerning LB in NENs and its role in clinical practice. We conducted a systematic review in July 2024 focusing on LB applications in NENs, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), micro RNA (miRNA), messenger RNA (mRNA) and extracellular vesicles. Sixty-five relevant articles were analysed. The LB showed potential in diagnosing and monitoring NENs. While CTCs face limitations due to low shedding, ctDNA provides valuable information on high-grade neoplasms. MiRNA and mRNA (e.g., the NETest) offer high sensitivity and specificity for diagnosis and prognosis, outperforming traditional markers like chromogranin A. The LB has significant potential for NEN diagnosis and monitoring but lacks widespread clinical integration due to limited prospective studies and guidelines, requiring further validation. Advances in sequencing technologies may enhance the clinical utility of LB in NENs. Future research should focus on refining LB methods, standardising protocols and exploring applications in high-grade NENs. Full article
(This article belongs to the Special Issue Updates in Neuroendocrine Neoplasms)
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