RARE DISEASE
Jejunal neuroendocrine tumor
Jejunal neuroendocrine tumor
Jejunal neuroendocrine tumor
Synonyms: Jejunal neuroendocrine neoplasm
Synonyms: Jejunal neuroendocrine neoplasm
Synonyms: Jejunal neuroendocrine neoplasm
Drug discovery
0
drugs
With orphan designations
Overview
Jejunal neuroendocrine tumors (NETs) are rare, malignant epithelial neoplasms arising from enterochromaffin cells, often presenting with nonspecific abdominal symptoms (cramping, obstruction) or advanced-stage carcinoid syndrome (flushing, diarrhea) [4][9]. These tumors demonstrate variable aggressiveness, with G1/G2 grading in most cases but potential for peritoneal carcinomatosis and distant metastases [1][6][15]. Diagnosis requires histopathology, chromogranin A testing, and somatostatin receptor imaging [10][15].
Categories: rare endocrine diseases, rare gastroenterological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
81 drug discovery papers about Jejunal neuroendocrine tumor, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
81 drug discovery papers about Jejunal neuroendocrine tumor, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-02-22 | Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms.
BACKGROUND: Disruption of the Men1 locus in epithelial and endocrine tissues fails to generate the full spectrum of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), raising the possibility of a potential stromal source for these cancers. Neural crest-derived glial cells were previously implicated in neuroendocrine tumors arising in the pituitary and pancreas, yet these studies lacked a clear mechanism for these events. Here, we investigated the hypothesis that Men1-driven Hedgehog (HH) signaling redirects the glial cell fate to give rise to neuroendocrine tumors in the gastrointestinal tract. METHODS: Hyperactivation of the HH signaling pathway in human GEP-NETs was evaluated using immunofluorescent staining and clinicogenomic databases. Men1 was deleted in the glial lineage by expressing Cre recombinase downstream of the human GFAP and Sox10 promoters. Overexpression of HH signaling proteins in mouse GEP-NETs was confirmed by immunofluorescent staining and immunoblot analysis. We generated human and mouse GEP-NET tumoroids and exposed them to agonists and inhibitors of HH signaling. HH activation of Men1-deficient glial cells was blocked by deleting the gene encoding primary ciliary protein KIF3A required for transducing SHH signaling. RESULTS: We demonstrated that human GEP-NETs overexpress HH signaling pathway components, including SHH and its cognate receptor PTCH1. We showed that patient-derived GEP-NET tumoroids proliferate in response to SHH pathway agonists. In contrast, pharmacologic inhibition of GLI1/2, but not inhibition of SMO alone, attenuated tumoroid growth. Genetic deletion of Men1 in GFAP+ and SOX10+ glial cells caused the development of pancreatic and intestinal NETs that overexpress HH proteins. Further use of tdTomato+ mice demonstrated the involvement of GFAP+ and SOX10+ glial cells in these tumors. Tumoroid cultures of mouse pancreatic, duodenal, and jejunal NETs recapitulated the drug response shown by patient-derived tumoroids. Lastly, Men1-deficient enteric glial cultures showed a glial-to-neuroendocrine transition that was alleviated upon HH inhibition, and these events were reproduced in genetic mice harboring GFAP+ cells with impaired primary cilia. CONCLUSIONS: Our study implicates the HH signaling pathway in GEP-NET development and underscores a glial cell of origin for these tumors.
2025-12-08 | Synchronous small bowel neuroendocrine tumour, colonic adenocarcinoma, and non-Hodgkin lymphoma: a rare triad of primary malignancies.
A man in his 70s presented to the Emergency Department with a history of progressive dyspnoea and was found to be anaemic. Endoscopic evaluation revealed a caecal lesion, confirmed histologically as a moderately differentiated adenocarcinoma. Staging computed-tomography imaging demonstrated widespread lymphadenopathy including pelvic, mediastinal and axillary regions, that appeared unlikely to be related to the colonic primary. Surgical resection of the right colon and a palpable axillary node was performed, during which a separate jejunal lesion was incidentally identified and resected. Histopathological analysis confirmed three distinct neoplasms: colonic adenocarcinoma, a small bowel neuroendocrine tumour, and non-Hodgkin lymphoma. Immunohistochemical and molecular profiling confirmed independent origins with no shared clonal relationship. The following case highlights the diagnostic and therapeutic challenges posed by synchronous multiple primary malignancies, particularly across divergent tissue lineages. Accurate histopathological distinction and multidisciplinary coordination are essential to guide management, prioritize treatment, and optimize patient outcomes in such exceptional presentations.
2024-12-23 | Analysis of dosimetry and clinical variables in treatments of neuroendocrine tumours with [177Lu]Lu-DOTA-TATE.
The main objectives were to study differences between the first and the fourth cycle in dosimetry variables in patients treated for neuroendocrine tumours with four cycles of [177Lu]Lu-DOTA-TATE, as well as to look for absorbed dose-effect correlations aiming to help individualise and optimise this therapy for future patients. SPECT/CT based dosimetry of tumour lesions and kidneys was performed in the first and the fourth cycles of the [177Lu]Lu-DOTA-TATE treatments for 17 patients from 2020 to 2023. Clinical variables of interest were collected in order to look for correlations with some dosimetry variables. Statistical analysis was performed using the R software. Regarding dosimetry variables, for lesions a significant decrease in absorbed dose, mass and initial activity between the first and fourth cycles was observed. For kidneys, a significant increase in absorbed dose was observed. Effective decay constants did not significantly change neither for lesions nor for kidneys. The relative decrease in lesion masses correlated with their total absorbed dose. Total absorbed doses to kidneys were well below the toxicity limits mostly used in this therapy. Relative decrease in lesion absorbed doses was significantly lower for tumour primary sites in ileum and jejunum compared to those in pancreas. Moreover, radiological response correlated with clinical response. The results seem to indicate that the current treatment scheme could be optimised in order to obtain better treatment outcomes.
2023-08-22 | Nuclear Imaging and Therapy
This thesis explores new applications of nuclear imaging and therapy in patients with hepatocellular carcinoma (HCC) and neuroendocrine tumors (NET). These diseases are often detected late, making curative therapy not always possible. Developments in positron emission tomography (PET) and radionuclide therapy have led to new nuclear agents. The aim of this thesis is to provide insight into several new applications of current and new tracers in the diagnosis and treatment of HCC and NET.One of the investigated tracers is 18F-DOPA, which is currently used for NET tumors that are negative on 68Ga-labeled somatostatin analog (SSA) PET scans. Our study confirms the equivalent detection of 18F-DOPA in tumor detection compared to 68Ga-SSAs. Selective internal radiation therapy (SIRT) uses yttrium-90 radioactive resin spheres that are intravascularly injected into the liver. Higher than usual dosages (>120 Gy) appear to lead to better results in tumor reduction and the effects not only seem to be greater but also longer lasting.Furthermore, we demonstrated that 11C-Choline and 18F-FDG together find more tumors that are relevant for clinical decision-making in patients suspected of HCC recurrence. The thesis also offers two prospective study protocols, namely a comparison of 68Ga-DOTA-TOC with the new somatostatin tracer 18F-SiTATE in NET and a comparison of ablation with SIRT as a bridge strategy in liver transplantation. These results suggest that broader use of 18F-DOPA in PET diagnosis of NET is possible and that higher tumor-targeted dosages in SIRT can lead to better treatment.
2022-06-13 | The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms
Gastroenteropancreatic neuroendocrine neoplasms feature high heterogeneity. Neuroendocrine tumor cells are closely associated with the tumor microenvironment. Tumor-infiltrating immune cells are mutually educated by each other and by tumor cells. Immune cells have dual protumorigenic and antitumorigenic effects. The immune environment is conducive to the invasion and metastasis of the tumor; in turn, tumor cells can change the immune environment. These cells also form cytokines, immune checkpoint systems, and tertiary lymphoid structures to participate in the process of mutual adaptation. Additionally, the fibroblasts, vascular structure, and microbiota exhibit interactions with tumor cells. From bench to bedside, clinical practice related to the tumor microenvironment is also regarded as promising. Targeting immune components and angiogenic regulatory molecules has been shown to be effective. The clinical efficacy of immune checkpoint inhibitors, adoptive cell therapy, and oncolytic viruses remains to be further discussed in clinical trials. Moreover, combination therapy is feasible for advanced high-grade tumors. The regulation of the tumor microenvironment based on multiple omics results can suggest innovative therapeutic strategies to prevent tumors from succeeding in immune escape and to support antitumoral effects.
2026-02-22 | Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms.
BACKGROUND: Disruption of the Men1 locus in epithelial and endocrine tissues fails to generate the full spectrum of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), raising the possibility of a potential stromal source for these cancers. Neural crest-derived glial cells were previously implicated in neuroendocrine tumors arising in the pituitary and pancreas, yet these studies lacked a clear mechanism for these events. Here, we investigated the hypothesis that Men1-driven Hedgehog (HH) signaling redirects the glial cell fate to give rise to neuroendocrine tumors in the gastrointestinal tract. METHODS: Hyperactivation of the HH signaling pathway in human GEP-NETs was evaluated using immunofluorescent staining and clinicogenomic databases. Men1 was deleted in the glial lineage by expressing Cre recombinase downstream of the human GFAP and Sox10 promoters. Overexpression of HH signaling proteins in mouse GEP-NETs was confirmed by immunofluorescent staining and immunoblot analysis. We generated human and mouse GEP-NET tumoroids and exposed them to agonists and inhibitors of HH signaling. HH activation of Men1-deficient glial cells was blocked by deleting the gene encoding primary ciliary protein KIF3A required for transducing SHH signaling. RESULTS: We demonstrated that human GEP-NETs overexpress HH signaling pathway components, including SHH and its cognate receptor PTCH1. We showed that patient-derived GEP-NET tumoroids proliferate in response to SHH pathway agonists. In contrast, pharmacologic inhibition of GLI1/2, but not inhibition of SMO alone, attenuated tumoroid growth. Genetic deletion of Men1 in GFAP+ and SOX10+ glial cells caused the development of pancreatic and intestinal NETs that overexpress HH proteins. Further use of tdTomato+ mice demonstrated the involvement of GFAP+ and SOX10+ glial cells in these tumors. Tumoroid cultures of mouse pancreatic, duodenal, and jejunal NETs recapitulated the drug response shown by patient-derived tumoroids. Lastly, Men1-deficient enteric glial cultures showed a glial-to-neuroendocrine transition that was alleviated upon HH inhibition, and these events were reproduced in genetic mice harboring GFAP+ cells with impaired primary cilia. CONCLUSIONS: Our study implicates the HH signaling pathway in GEP-NET development and underscores a glial cell of origin for these tumors.
2025-12-08 | Synchronous small bowel neuroendocrine tumour, colonic adenocarcinoma, and non-Hodgkin lymphoma: a rare triad of primary malignancies.
A man in his 70s presented to the Emergency Department with a history of progressive dyspnoea and was found to be anaemic. Endoscopic evaluation revealed a caecal lesion, confirmed histologically as a moderately differentiated adenocarcinoma. Staging computed-tomography imaging demonstrated widespread lymphadenopathy including pelvic, mediastinal and axillary regions, that appeared unlikely to be related to the colonic primary. Surgical resection of the right colon and a palpable axillary node was performed, during which a separate jejunal lesion was incidentally identified and resected. Histopathological analysis confirmed three distinct neoplasms: colonic adenocarcinoma, a small bowel neuroendocrine tumour, and non-Hodgkin lymphoma. Immunohistochemical and molecular profiling confirmed independent origins with no shared clonal relationship. The following case highlights the diagnostic and therapeutic challenges posed by synchronous multiple primary malignancies, particularly across divergent tissue lineages. Accurate histopathological distinction and multidisciplinary coordination are essential to guide management, prioritize treatment, and optimize patient outcomes in such exceptional presentations.
2024-12-23 | Analysis of dosimetry and clinical variables in treatments of neuroendocrine tumours with [177Lu]Lu-DOTA-TATE.
The main objectives were to study differences between the first and the fourth cycle in dosimetry variables in patients treated for neuroendocrine tumours with four cycles of [177Lu]Lu-DOTA-TATE, as well as to look for absorbed dose-effect correlations aiming to help individualise and optimise this therapy for future patients. SPECT/CT based dosimetry of tumour lesions and kidneys was performed in the first and the fourth cycles of the [177Lu]Lu-DOTA-TATE treatments for 17 patients from 2020 to 2023. Clinical variables of interest were collected in order to look for correlations with some dosimetry variables. Statistical analysis was performed using the R software. Regarding dosimetry variables, for lesions a significant decrease in absorbed dose, mass and initial activity between the first and fourth cycles was observed. For kidneys, a significant increase in absorbed dose was observed. Effective decay constants did not significantly change neither for lesions nor for kidneys. The relative decrease in lesion masses correlated with their total absorbed dose. Total absorbed doses to kidneys were well below the toxicity limits mostly used in this therapy. Relative decrease in lesion absorbed doses was significantly lower for tumour primary sites in ileum and jejunum compared to those in pancreas. Moreover, radiological response correlated with clinical response. The results seem to indicate that the current treatment scheme could be optimised in order to obtain better treatment outcomes.
2023-08-22 | Nuclear Imaging and Therapy
This thesis explores new applications of nuclear imaging and therapy in patients with hepatocellular carcinoma (HCC) and neuroendocrine tumors (NET). These diseases are often detected late, making curative therapy not always possible. Developments in positron emission tomography (PET) and radionuclide therapy have led to new nuclear agents. The aim of this thesis is to provide insight into several new applications of current and new tracers in the diagnosis and treatment of HCC and NET.One of the investigated tracers is 18F-DOPA, which is currently used for NET tumors that are negative on 68Ga-labeled somatostatin analog (SSA) PET scans. Our study confirms the equivalent detection of 18F-DOPA in tumor detection compared to 68Ga-SSAs. Selective internal radiation therapy (SIRT) uses yttrium-90 radioactive resin spheres that are intravascularly injected into the liver. Higher than usual dosages (>120 Gy) appear to lead to better results in tumor reduction and the effects not only seem to be greater but also longer lasting.Furthermore, we demonstrated that 11C-Choline and 18F-FDG together find more tumors that are relevant for clinical decision-making in patients suspected of HCC recurrence. The thesis also offers two prospective study protocols, namely a comparison of 68Ga-DOTA-TOC with the new somatostatin tracer 18F-SiTATE in NET and a comparison of ablation with SIRT as a bridge strategy in liver transplantation. These results suggest that broader use of 18F-DOPA in PET diagnosis of NET is possible and that higher tumor-targeted dosages in SIRT can lead to better treatment.
2022-06-13 | The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms
Gastroenteropancreatic neuroendocrine neoplasms feature high heterogeneity. Neuroendocrine tumor cells are closely associated with the tumor microenvironment. Tumor-infiltrating immune cells are mutually educated by each other and by tumor cells. Immune cells have dual protumorigenic and antitumorigenic effects. The immune environment is conducive to the invasion and metastasis of the tumor; in turn, tumor cells can change the immune environment. These cells also form cytokines, immune checkpoint systems, and tertiary lymphoid structures to participate in the process of mutual adaptation. Additionally, the fibroblasts, vascular structure, and microbiota exhibit interactions with tumor cells. From bench to bedside, clinical practice related to the tumor microenvironment is also regarded as promising. Targeting immune components and angiogenic regulatory molecules has been shown to be effective. The clinical efficacy of immune checkpoint inhibitors, adoptive cell therapy, and oncolytic viruses remains to be further discussed in clinical trials. Moreover, combination therapy is feasible for advanced high-grade tumors. The regulation of the tumor microenvironment based on multiple omics results can suggest innovative therapeutic strategies to prevent tumors from succeeding in immune escape and to support antitumoral effects.
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