Gastroenteropancreatic neuroendocrine neoplasm: Research & Drug Discovery Data

Drug discovery

drugs

With orphan designations

Overview

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors arising from neuroendocrine cells in the gastrointestinal tract and pancreas. Classified as well-differentiated (NETs) or poorly differentiated (NECs), they range from indolent to aggressive. Functional tumors secrete hormones (e.g., insulin, gastrin), causing syndromes like carcinoid or Zollinger-Ellison, while non-functional tumors present with mass effects or metastases. Diagnosis integrates biomarkers (chromogranin A), imaging (somatostatin receptor PET), and histopathology (Ki-67 index). Treatment is multimodal, involving surgery, somatostatin analogs, peptide receptor radionuclide therapy (PRRT), targeted agents (everolimus, sunitinib), and chemotherapy (CAPTEM) based on grade, stage, and functionality [1][4][11][18].

Population

Annual incidence: 3.5–5.4/100,000 in North America, rising due to improved diagnostics [1][7][12].
Median age at diagnosis: 5th decade; slight male predominance in some regions [1][6][12].
Common sites: Small intestine, rectum, pancreas; 10% linked to hereditary syndromes (MEN1, VHL) [1][4][12].

Burden

Metastatic at diagnosis: ~50% (liver metastases in 82% of advanced cases) [1][7][12].
Functional tumors: Chronic symptoms (diarrhea, flushing) reduce quality of life [14][16].
5-year survival: 35% for metastatic well-differentiated NETs vs. 4% for NECs [1][7][12].

Therapies

Localized disease: Surgery (curative intent); adjuvant therapy if high Ki-67 [3][8][18].
Advanced disease:
- SSAs (octreotide, lanreotide) for symptom/oncologic control [3][13][18].
- PRRT (177Lu-DOTATATE) for SSTR-positive tumors [18][20].
- Targeted agents (everolimus, sunitinib) or chemotherapy (CAPTEM) for pancreatic/aggressive NETs [3][8][11].
NECs: Platinum-etoposide chemotherapy [8][18].

Categories: rare endocrine diseases, rare neoplastic diseases

Research Papers

1,415 drug discovery papers related to Gastroenteropancreatic neuroendocrine neoplasm, with 4 first-in-class and 7 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:

2026-07-09 | The Genetics and Screening of Gastroenteropancreatic Neuroendocrine Tumors and Adrenal Tumors.

Management of adrenal tumors and neuroendocrine tumors (NETs) requires careful discussion on whether resection with curative intent is worth the risk of surgical morbidity and risk of endocrine morbidity requiring exogenous hormonal replacement. Such deliberations are important in germline-associated NETs and adrenal tumors because of the multifocal nature of the disease. Identifying patients with germline mutations will encourage screening and surveillance to be more frequent compared to patients with sporadic-associated mutations. With improvements in molecular profiling, mutational patterns are more efficiently detected, allowing for more individualized treatment plans and potential future targeted therapies.

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2026-06-26 | Review of Haematological Toxicities in Well-Differentiated Neuroendocrine Tumours: A Case Report and Comprehensive Review of the Literature.

Background: Neuroendocrine tumours (NETs) are heterogeneous neoplasms with several treatment options. Response rates, disease progression, and haematological toxicities can limit the use of some indicated treatments. Case Presentation: A 73-year-old woman with a well-differentiated grade 2 pancreatic NET (Ki-67 18%) underwent surgical resection and later developed hepatic recurrence. First-line treatment with sunitinib plus octreotide achieved temporary disease stabilisation. Upon progression, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE was initiated, resulting in stable disease but complicated by grade 3 thrombocytopenia. Two years later, PRRT retreatment was performed due to disease progression, which led to grade 4 thrombocytopenia. Further treatments with capecitabine and everolimus were limited by progression and significant thrombocytopenia. Therapy was switched to streptozocin plus 5-fluorouracil, which resulted in recovery of platelet counts, absence of haematological toxicity, and a sustained radiologic response until March 2025, when she presented with hepatic progression. FOLFOX chemotherapy was initiated but discontinued after one cycle due to severe thrombocytopenia. Deterioration in general condition ultimately led to supportive care and death in March 2026. Conclusions: This case highlights the risk of cumulative haematological toxicity with PRRT, particularly in retreatment settings. Careful patient selection and close monitoring are essential. Streptozocin-based chemotherapy may be an effective and well-tolerated alternative for patients with treatment-limiting toxicity.

Open article ↗

2026-07-09 | The Genetics and Screening of Gastroenteropancreatic Neuroendocrine Tumors and Adrenal Tumors.

Open article ↗

2026-06-26 | Review of Haematological Toxicities in Well-Differentiated Neuroendocrine Tumours: A Case Report and Comprehensive Review of the Literature.

Open article ↗

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Drug Discovery Landscape

20 orphan drug designations for Gastroenteropancreatic neuroendocrine neoplasm, including 6 approved therapies.

Drug	Therapy type	Regulator	Orphan designation	Approval	Sponsor
Lutetium-177(3+),S2,S7-cyclo[N-{4,7,10-tricarboxymethyl-1,4,7,10-tetraaza-cyclododecan-1-yl-acetyl}-4-chloro-L-phenylalanyl-D-cysteinyl-4-[(4S)-2,6-dioxo-1,3-diazinane-4-carboxamido]-L-phenylalanyl-4-(carbamoylamino)-D-phenylalanyl-L-lysyl-L-threonyl-L-cysteinyl-D-tyrosinamide]	small molecules	EMA	2016-10-14	—	Ariceum Therapeutics GmbH
FOSBRETABULIN TROMETHAMINE	small molecules	EMA	2016-03-21	—	Diamond Pharma Services Ireland Limited
Ceclazepide	small molecules	EMA	2015-12-14	—	Yes Pharmaceutical Development Services GmbH
lutetium (177Lu)-edotreotide	peptides	FDA	2015-05-21	—	ITM Solucin GmbH
Gallium (68Ga)-edotreotide [SomaKit TOC]	peptides	EMA	2015-03-19	2016-12-12	Novartis Europharm Limited
satoreotide tetraxetan	peptides	FDA	2014-09-24	—	Ariceum Therapeutics GmbH
Lutetium (177Lu) edotreotide	peptides	EMA	2014-06-04	—	ITM Solucin GmbH
68Ga-2,2'-(7-(4-((S)-1-((4S,7S,10S,13R,16S,19R)-4-((R)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylcarbamoyl)-10-(4-aminobutyl)-16-(4-((S)-2,6-dioxohexahydropyrimidine-4-carboxamido)benzyl)-7-((R)-1-hydroxyethyl)-6,9,12,15,18-pentaoxo-13-(4-ureidobenzyl)-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-19-ylamino)-3-(4-chlorophenyl)-1-oxopropan-2-ylamino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid	other	EMA	2014-02-19	—	Ariceum Therapeutics GmbH
Gallium [Ga-68]-N-[(4,7,10-tricarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-Lcysteinyl-L-threonine-cyclic(2-7)disulfide	other	EMA	2014-02-19	—	Advanced Accelerator Applications
Gallium (68Ga)-pasireotide tetraxetan	small molecules	EMA	2011-10-27	—	OctreoPharm Sciences GmbH
lutetium Lu 177 dotatate [Lutathera]	peptides	FDA	2009-01-12	2024-04-23	Advanced Accelerator Applications
lutetium Lu 177 dotatate [Lutathera]	peptides	FDA	2009-01-12	2024-04-23	Advanced Accelerator Applications
lutetium Lu 177 dotatate [Lutathera]	other	FDA	2009-01-12	2024-04-23	Advanced Accelerator Applications
lutetium Lu 177 dotatate	peptides	FDA	2009-01-12	2018-01-26	Advanced Accelerator Applications
Yttrium (90Y) edotreotide [Onalta 90Y edotreotide]	peptides	EMA	2008-12-04	—	[INACTIVE] Molecular Insight Limited
Lutetium (177Lu)-N-[(4,7,10-Tricarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-L-cysteinyl-L-threonine-cyclic(2-7)disulfide [Lutathera]	peptides	EMA	2008-01-31	2017-09-28	Novartis Europharm Limited
Everolimus [Afinitor]	small molecules	EMA	2007-11-14	—	Novartis Europharm Limited
Edotreotide	other	FDA	2005-07-28	—	Molecular Insight Pharmaceuticals, Inc. (Progenics Subsidiary)
Multi-ligand somatostatin analog	peptides	FDA	2004-07-27	—	Novartis Pharmaceuticals Corporation
Pasireotide	small molecules	EMA	2004-06-08	—	Novartis Europharm Limited

Gastroenteropancreatic neuroendocrine neoplasm

Gastroenteropancreatic neuroendocrine neoplasm

Gastroenteropancreatic neuroendocrine neoplasm

Overview

Population

Burden

Therapies

Categories: rare endocrine diseases, rare neoplastic diseases

Research Papers

2026-07-09 | The Genetics and Screening of Gastroenteropancreatic Neuroendocrine Tumors and Adrenal Tumors.

2026-06-26 | Review of Haematological Toxicities in Well-Differentiated Neuroendocrine Tumours: A Case Report and Comprehensive Review of the Literature.

2026-07-09 | The Genetics and Screening of Gastroenteropancreatic Neuroendocrine Tumors and Adrenal Tumors.

2026-06-26 | Review of Haematological Toxicities in Well-Differentiated Neuroendocrine Tumours: A Case Report and Comprehensive Review of the Literature.

Drug Discovery Landscape

Updated: Aug 5, 2026