Neuroendocrine neoplasm

Summary

Neuroendocrine neoplasm (MONDO:0019496) is a cancer (an umbrella term covering 14 Mondo subtypes) with 4 cohort genes (19 GWAS associations across 4 studies; 3 CIViC-evidence somatic drivers; 5 ClinVar predisposition records) and 451 clinical trials. Molecularly, KDR Overexpression confers sensitivity to Pazopanib in Neuroendocrine Tumor (CIViC Level B); 3 further subtype–drug associations are mapped below. Top therapeutic interventions include lutetium oxodotreotide lu-177, lanreotide, and edotreotide gallium ga-68.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (United States) [Orphanet-validated]
• Umbrella term: 14 Mondo subtypes
• Cohort genes: 4
• GWAS associations: 19
• ClinVar variants: 5
• Clinical trials: 451
• Precision-medicine evidence (CIViC): 4 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	2.53	Europe	Validated
Annual incidence	1-9 / 100 000	3.2	Norway	Validated
Annual incidence	1-9 / 100 000	5.25	United States	Validated
Point prevalence	1-5 / 10 000	35	United States	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	neuroendocrine neoplasm
Mondo ID	MONDO:0019496
EFO	EFO:1001901
MeSH	D018358
Orphanet	877
DOID	DOID:169
NCIT	C188218, C3809
SNOMED CT	255046005
UMLS	C0206754
MedGen	64652
GARD	0009316
Is cancer (heuristic)	yes

Also known as: APUDoma · neuroendocrine neoplasm · neuroendocrine tumor · neuroendocrine tumour

Data availability: 5 ClinVar variants · 19 GWAS associations (4 studies).

Disease family

An umbrella term covering 14 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › endocrine gland neoplasm › neuroendocrine neoplasm

Related subtypes (13): benign endocrine neoplasm, thymus neoplasm, granulosa cell tumor, thyroid tumor, pituitary tumor, familial tumoral calcinosis, malignant endocrine neoplasm, non-functioning endocrine neoplasm, functioning endocrine neoplasm, adrenal gland neoplasm, pineal body neoplasm, tumor of parathyroid gland, liver and intrahepatic bile duct neoplasm

Subtypes (14): paraganglioma, neuroendocrine carcinoma, prostate neuroendocrine neoplasm, ovarian neuroendocrine neoplasm, breast neuroendocrine neoplasm, carcinoid tumor, lung neuroendocrine neoplasm, laryngeal neuroendocrine neoplasm, middle ear neuroendocrine tumor, hereditary pheochromocytoma-paraganglioma, bronchial endocrine tumor, thymic neuroendocrine tumor, uterine corpus neuroendocrine neoplasm, digestive system neuroendocrine neoplasm

Genetics & variants

GWAS landscape

19 GWAS associations across 4 studies. Top hits map to 12 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs543107477	2e-13	MPP7	T	3.18
rs183808807	2e-13		T	3.77
rs183587406	4e-13	ITGB4	C	2.66
rs551907375	9e-13	ZCCHC24	G	3.4
rs192865481	1e-12	PPFIBP2	C	3.52
rs530143739	2e-12	ALPL	C	3.32
rs553574525	2e-12	MCTP1	A	3.4
rs555554410	3e-12	PMM2P2 - MIX23P3	T	3.52
rs528111636	4e-12	GATD3	C	4.74
rs184266990	1e-11	LINC03062	C	2.96
rs574144779	2e-11	YTHDF1 - BIRC7	T	2.07
rs535673445	2e-11	SLC35F3	G	3.01
rs140800961	2e-11	EXOC5P1 - LARP1BP1	C	4.01
rs28405676	2e-11	MIR4289 - PCNPP2	C	2.78
rs192006671	3e-11	RNU6-1120P - KCNMB2	T	3.62
rs542929735	3e-11	GCNT2	G	2.87
rs183021871	3e-11	SGPL1	C	3.51
rs551382130	4e-11	IGLL1 - DRICH1	G	3.52
rs188416553	4e-11	ALDH18A1	C	2.74

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST003785	Du Y	2016	832	4,542	Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.
GCST90477252	Verma A	2024	540	450,490	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479836	Verma A	2024	211	121,601	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481549	Verma A	2024	211	121,601	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	18

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	19
unknown	0

Functional consequences

Consequence	Count
intron_variant	13
intergenic_variant	4
3_prime_UTR_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs543107477	10	28051359	T>G	0	3_prime_UTR_variant	MPP7	2e-13	Tier 2: splice/UTR
rs183808807	16	72644283	T>A	0	intron_variant		2e-13	Tier 4: intronic/intergenic
rs183587406	17	75744841	C>T	0.001	intron_variant	ITGB4	4e-13	Tier 4: intronic/intergenic
rs551907375	10	79433550	G>A	0	intron_variant	ZCCHC24	9e-13	Tier 4: intronic/intergenic
rs192865481	11	7632531	C>T	0.001	intron_variant	PPFIBP2	1e-12	Tier 4: intronic/intergenic
rs530143739	1	21526208	C>T	0	intron_variant	ALPL	2e-12	Tier 4: intronic/intergenic
rs553574525	5	94910152	A>G	0	intron_variant	MCTP1	2e-12	Tier 4: intronic/intergenic
rs555554410	18	12196285	T>A	0	intergenic_variant	PMM2P2 - MIX23P3	3e-12	Tier 4: intronic/intergenic
rs528111636	21	44140704	C>T	0.001	intron_variant	GATD3	4e-12	Tier 4: intronic/intergenic
rs184266990	9	89725906	C>A,T	0.002	intron_variant	LINC03062	1e-11	Tier 4: intronic/intergenic
rs574144779	20	63225867	T>C,G	0.002	intergenic_variant	YTHDF1 - BIRC7	2e-11	Tier 4: intronic/intergenic
rs535673445	1	234077777	G>A	0.001	intron_variant	SLC35F3	2e-11	Tier 4: intronic/intergenic
rs140800961	4	62838520	C>A,G,T	0.001	intergenic_variant	EXOC5P1 - LARP1BP1	2e-11	Tier 4: intronic/intergenic
rs28405676	9	88778857	C>A,T	0.003	intron_variant	MIR4289 - PCNPP2	2e-11	Tier 4: intronic/intergenic
rs192006671	3	178036943	T>C	0	intron_variant	RNU6-1120P - KCNMB2	3e-11	Tier 4: intronic/intergenic
rs542929735	6	10599162	G>C	0	intron_variant	GCNT2	3e-11	Tier 4: intronic/intergenic
rs183021871	10	70913047	C>G	0.001	intergenic_variant	SGPL1	3e-11	Tier 4: intronic/intergenic
rs551382130	22	23607113	G>A,C	0	non_coding_transcript_exon_variant	IGLL1 - DRICH1	4e-11	Tier 4: intronic/intergenic
rs188416553	10	95630770	C>T	0.001	intron_variant	ALDH18A1	4e-11	Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 1 conflicting classifications of pathogenicity; other, 1 pathogenic, 1 conflicting classifications of pathogenicity; other; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
157519	NM_004064.5(CDKN1B):c.279_280insT (p.Pro94fs)	CDKN1B	Pathogenic	criteria provided, single submitter
157518	NM_004064.5(CDKN1B):c.127delinsTAA (p.Arg43Ter)	CDKN1B	Likely pathogenic	no assertion criteria provided
157520	NM_004064.5(CDKN1B):c.334del (p.Ser112fs)	CDKN1B	Likely pathogenic	no assertion criteria provided
10	NM_000410.4(HFE):c.187C>G (p.His63Asp)	HFE	Conflicting classifications of pathogenicity; other	criteria provided, conflicting classifications
9	NM_000410.4(HFE):c.845G>A (p.Cys282Tyr)	HFE	Conflicting classifications of pathogenicity; other; risk factor	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SSTR5			CIViC #5499
MGMT			CIViC #34
CDKN1B	LoF	BRCA,HCC,PCM,PRAD,SIC	CIViC #914

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MGMT	Orphanet:251576	Gliosarcoma
MGMT	Orphanet:251579	Giant cell glioblastoma
MGMT	Orphanet:618	Familial melanoma
CDKN1B	Orphanet:276152	Multiple endocrine neoplasia type 4
CDKN1B	Orphanet:652	Multiple endocrine neoplasia type 1
HFE	Orphanet:443057	Sporadic porphyria cutanea tarda
HFE	Orphanet:443062	Familial porphyria cutanea tarda
HFE	Orphanet:465508	Symptomatic form of HFE-related hemochromatosis
HFE	Orphanet:586	Cystic fibrosis
HFE	Orphanet:648581	Digenic hemochromatosis

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SSTR5	HGNC:11334	ENSG00000162009	P35346	Somatostatin receptor type 5	civic_evidence
MGMT	HGNC:7059	ENSG00000170430	P16455	Methylated-DNA–protein-cysteine methyltransferase	civic_evidence
CDKN1B	HGNC:1785	ENSG00000111276	P46527	Cyclin-dependent kinase inhibitor 1B	clinvar
HFE	HGNC:4886	ENSG00000010704	Q30201	Hereditary hemochromatosis protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SSTR5	Somatostatin receptor type 5	Receptor for somatostatin 28 and to a lesser extent for somatostatin-14.
MGMT	Methylated-DNA–protein-cysteine methyltransferase	Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA.
CDKN1B	Cyclin-dependent kinase inhibitor 1B	Important regulator of cell cycle progression.
HFE	Hereditary hemochromatosis protein	Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.75

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	7.3×	0.314
GPCR	1	6.0×	0.314
Enzyme (other)	1	3.0×	0.392
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SSTR5	GPCR	yes		GPCR_Rhodpsn, Somatstn_rcpt, Somatstn_rcpt_5
MGMT	Enzyme (other)	yes	2.1.1.63	MethylDNA_cys_MeTrfase_AS, MethylG_MeTrfase_N, MethylDNA_cys_MeTrfase_DNA-bd
CDKN1B	Other/Unknown	no		CDI_dom, CDI_dom_sf
HFE	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac atrium	1
right atrium auricular region	1
tendon of biceps brachii	1
endometrium epithelium	1
liver	1
right lobe of liver	1
pigmented layer of retina	1
retina	1
ventricular zone	1
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SSTR5	75	tissue_specific	yes	tendon of biceps brachii, right atrium auricular region, cardiac atrium
MGMT	261	ubiquitous	marker	right lobe of liver, liver, endometrium epithelium
CDKN1B	301	ubiquitous	marker	pigmented layer of retina, retina, ventricular zone
HFE	238	ubiquitous	marker	type B pancreatic cell, olfactory bulb, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDKN1B	4,635
MGMT	2,853
HFE	1,569
SSTR5	156

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MGMT	P16455	23
CDKN1B	P46527	19
SSTR5	P35346	7
HFE	Q30201	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 63. Enrichment computed across 4 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MGMT-mediated DNA damage reversal	1	2855.0×	0.022	MGMT
PTK6 Regulates Cell Cycle	1	475.8×	0.031	CDKN1B
DNA Damage Reversal	1	407.9×	0.031	MGMT
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1	219.6×	0.031	CDKN1B
AKT phosphorylates targets in the cytosol	1	203.9×	0.031	CDKN1B
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	178.4×	0.031	CDKN1B
p53-Dependent G1 DNA Damage Response	1	178.4×	0.031	CDKN1B
p53-Dependent G1/S DNA damage checkpoint	1	178.4×	0.031	CDKN1B
G1/S DNA Damage Checkpoints	1	167.9×	0.031	CDKN1B
FOXO-mediated transcription of cell cycle genes	1	167.9×	0.031	CDKN1B
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	1	158.6×	0.031	CDKN1B
RHO GTPases activate CIT	1	150.3×	0.031	CDKN1B
TP53 Regulates Transcription of Cell Cycle Genes	1	135.9×	0.031	CDKN1B
Signaling by PTK6	1	135.9×	0.031	CDKN1B
Signaling by Non-Receptor Tyrosine Kinases	1	135.9×	0.031	CDKN1B
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	109.8×	0.031	CDKN1B
Constitutive Signaling by AKT1 E17K in Cancer	1	105.7×	0.031	CDKN1B
Aberrant regulation of mitotic cell cycle due to RB1 defects	1	102.0×	0.031	CDKN1B
G1 Phase	1	98.5×	0.031	CDKN1B
Diseases of mitotic cell cycle	1	98.5×	0.031	CDKN1B
PI3K/AKT Signaling in Cancer	1	92.1×	0.031	CDKN1B
Transferrin endocytosis and recycling	1	92.1×	0.031	HFE
FLT3 Signaling	1	86.5×	0.031	CDKN1B
FOXO-mediated transcription	1	84.0×	0.031	CDKN1B
Cyclin E associated events during G1/S transition	1	71.4×	0.035	CDKN1B
Cyclin A:Cdk2-associated events at S phase entry	1	66.4×	0.036	CDKN1B
G1/S Transition	1	58.3×	0.038	CDKN1B
Cyclin D associated events in G1	1	58.3×	0.038	CDKN1B
SCF(Skp2)-mediated degradation of p27/p21	1	51.9×	0.042	CDKN1B
Mitotic G1 phase and G1/S transition	1	46.0×	0.044	CDKN1B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I	1	4213.0×	0.008	HFE
regulation of iron ion transport	1	2106.5×	0.008	HFE
regulation of lens fiber cell differentiation	1	2106.5×	0.008	CDKN1B
negative regulation of cardiac muscle tissue regeneration	1	2106.5×	0.008	CDKN1B
response to iron ion starvation	1	1404.3×	0.010	HFE
negative regulation of CD8-positive, alpha-beta T cell activation	1	1053.2×	0.010	HFE
autophagic cell death	1	842.6×	0.010	CDKN1B
negative regulation of epithelial cell proliferation involved in prostate gland development	1	702.2×	0.010	CDKN1B
negative regulation of T cell cytokine production	1	601.9×	0.010	HFE
cellular response to antibiotic	1	601.9×	0.010	CDKN1B
cellular response to iron ion	1	601.9×	0.010	HFE
epithelial cell proliferation involved in prostate gland development	1	526.6×	0.010	CDKN1B
regulation of protein localization to cell surface	1	421.3×	0.010	HFE
DNA alkylation repair	1	383.0×	0.010	MGMT
transferrin transport	1	383.0×	0.010	HFE
urate metabolic process	1	383.0×	0.010	HFE
nuclear export	1	383.0×	0.010	CDKN1B
positive regulation of peptide hormone secretion	1	383.0×	0.010	HFE
regulation of cell cycle G1/S phase transition	1	383.0×	0.010	CDKN1B
hormone biosynthetic process	1	351.1×	0.010	HFE
regulation of exit from mitosis	1	300.9×	0.010	CDKN1B
negative regulation of epithelial cell apoptotic process	1	300.9×	0.010	CDKN1B
negative regulation of cell population proliferation	2	21.1×	0.010	SSTR5, CDKN1B
cellular response to lithium ion	1	280.9×	0.010	CDKN1B
response to iron ion	1	234.1×	0.012	HFE
epithelial cell apoptotic process	1	210.7×	0.012	CDKN1B
negative regulation of ubiquitin-dependent protein catabolic process	1	210.7×	0.012	HFE
negative regulation of mitotic cell cycle	1	200.6×	0.012	CDKN1B
positive regulation of receptor-mediated endocytosis	1	200.6×	0.012	HFE
regulation of cyclin-dependent protein serine/threonine kinase activity	1	183.2×	0.013	CDKN1B

Therapeutics

Drugs indicated for this disease

3 approved, 7 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Avelumab	Approved (phase 4)
Everolimus	Approved (phase 4)
Sunitinib	Approved (phase 4)
Capecitabine	Phase 3 (in late-stage trials)
Edotreotide	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Guanidine	Phase 3 (in late-stage trials)
Octreotide	Phase 3 (in late-stage trials)
Streptozocin	Phase 3 (in late-stage trials)
Surufatinib	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alectinib, Bevacizumab, Cabozantinib, Dacarbazine, Dordaviprone, Doxorubicin, Entinostat, Erlotinib, Fosbretabulin, Interferon Alfa, Ipilimumab, Lanreotide, Lenvatinib, Lithium Carbonate, Metformin, Nintedanib, Nivolumab, Novaferon, Oxaliplatin, Panobinostat, Pasireotide, Patupilone, Pazopanib, Pembrolizumab, Pemetrexed, Pentetreotide, Retifanlimab, Ribociclib, Sintilimab, Sorafenib, Tamoxifen, Tegafur, Telotristat, Telotristat Ethyl, Temozolomide, Tetraxetan, Thalidomide, Triapine, Vatalanib.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 3 of 4 evidence-associated genes (75%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SSTR5	LANREOTIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SSTR5	11	4
MGMT	2	3
CDKN1B	0	0
HFE	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LANREOTIDE	4	SSTR5
OCTREOTIDE	4	SSTR5
GALLIUM OXODOTREOTIDE	4	SSTR5
ASTEMIZOLE	4	SSTR5
PASIREOTIDE	4	SSTR5
LOPERAMIDE	4	SSTR5
SOMATOSTATIN	3	SSTR5
VAPREOTIDE	3	SSTR5
EDOTREOTIDE	3	SSTR5
6-O-BENZYLGUANINE	3	MGMT
SEGLITIDE	2	SSTR5
EDOTREOTIDE YTTRIUM	2	SSTR5
LOMEGUATRIB	2	MGMT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SSTR5	151	Binding:123, Functional:24, ADMET:4
MGMT	86	Binding:84, ADMET:2
CDKN1B	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MGMT	2.1.1.63	methylated-DNA-[protein]-cysteine S-methyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SSTR5	151

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

10 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
GALLIUM OXODOTREOTIDE	4	SSTR5
ASTEMIZOLE	4	SSTR5
LOPERAMIDE	4	SSTR5
SOMATOSTATIN	3	SSTR5
VAPREOTIDE	3	SSTR5
EDOTREOTIDE	3	SSTR5
6-O-BENZYLGUANINE	3	MGMT
SEGLITIDE	2	SSTR5
EDOTREOTIDE YTTRIUM	2	SSTR5
LOMEGUATRIB	2	MGMT

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SSTR5
B	Phased (≥1) drug, not yet approved	1	MGMT
C	Druggable family + PDB, no drug	1	HFE
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CDKN1B

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CDKN1B	5	—
HFE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 451.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	163
PHASE2	143
PHASE1	52
PHASE1/PHASE2	36
PHASE3	25
EARLY_PHASE1	16
PHASE4	9
PHASE2/PHASE3	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06485739	PHASE4	NOT_YET_RECRUITING	Irinotecan Liposomes for the Treatment of Neuroendocrine Carcinoma
NCT07272512	PHASE4	RECRUITING	Prospective Multicenter Real-world Study of Surufatinib in Patients With Advanced Neuroendocrine Neoplasms
NCT01317615	PHASE4	COMPLETED	RAD001 With Paclitaxel and Carboplatin in First Line Treatment of Patients With Advanced Large Cell Lung Cancer With Neuroendocrine Differentiation
NCT01595009	PHASE4	COMPLETED	An Open-label, Multi-center, Expanded Access Study of Everolimus in Participants With Advanced Neuroendocrine Tumors (NETs) (Core Study) and an Extension Study to the Open-label, Multi-center, Expanded Access Study of Everolimus in Patients With Advanced NETs (E1)
NCT01794793	PHASE4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT02075606	PHASE4	COMPLETED	Circulating Tumour Cells in Somatuline Autogel Treated NeuroEndocrine Tumours Patients
NCT03083210	PHASE4	UNKNOWN	Study of Lanreotide in Metastatic or Recurrent Grade I-II Hindgut NET
NCT03289741	PHASE4	COMPLETED	A Study to Evaluate Patient Experience in the Therapy of Neuroendocrine Tumors Treated With Octreotide Long Acting Release Versus Lanreotide
NCT04140409	PHASE4	TERMINATED	Sandostatin (Octreotide LAR) May Lead to Clinical Improvement Through Receptor Occupation Optimisation
NCT00569127	PHASE3	ACTIVE_NOT_RECRUITING	Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor
NCT03049189	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients
NCT03375320	PHASE3	ACTIVE_NOT_RECRUITING	Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors
NCT04706910	PHASE3	RECRUITING	18F-DOPA II - PET Imaging Optimization
NCT04810091	PHASE3	ACTIVE_NOT_RECRUITING	Telotristat Ethyl for the Treatment of Carcinoid Heart Disease in Patients With Metastatic Neuroendocrine Tumor
NCT04847505	PHASE3	RECRUITING	68Ga-DOTA-TATE PET/CT Imaging in NETs
NCT04919226	PHASE3	ACTIVE_NOT_RECRUITING	Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE
NCT05387603	PHASE3	RECRUITING	Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.
NCT05459844	PHASE3	ACTIVE_NOT_RECRUITING	A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs
NCT05477576	PHASE3	RECRUITING	Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy
NCT05918302	PHASE3	RECRUITING	Efficacy and Safety of Radiotherapy Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus.
NCT06398444	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of Lutetium[177Lu] Oxodotreotide Injection in Patients With Advanced Neuroendocrine Neoplasms
NCT06855095	PHASE2/PHASE3	RECRUITING	Absorbed Tumor Dose in Peptide Receptor Radionuclide Therapy with Long-acting Somatostatin Analogues - ATSA Trial
NCT00037869	PHASE3	COMPLETED	High Dose I-131 Metaiodobenzylguanidine(MIBG) for Metastatic Neuroendocrine Tumors
NCT00171873	PHASE3	COMPLETED	Antiproliferative Effect of Octreotide in Patients With Metastasized Neuroendocrine Tumors of the Midgut
NCT00227136	PHASE3	TERMINATED	Effect of Oral 5-HTP Intake on Urinary 5-HIAA Excretion
NCT00227617	PHASE2/PHASE3	TERMINATED	Combination Chemotherapy and Bevacizumab in Treating Patients With Advanced Neuroendocrine Tumors
NCT00442533	PHASE2/PHASE3	COMPLETED	Safety and Efficacy Study of In-111 Pentetreotide to Treat Neuroendocrine Tumors
NCT01524783	PHASE3	COMPLETED	Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin)
NCT01578239	PHASE3	COMPLETED	A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours
NCT01744249	PHASE2/PHASE3	COMPLETED	Sandostatin LAR and Axitinib vs Pbo in Pnts With Advanced Well-differentiated Non-pancreatic Neuroendocrine Carcinomas
NCT01755182	PHASE3	TERMINATED	Systemic Therapy With or Without Upfront Transarterial Embolization for Inoperable Liver Metastasis of Neuroendocrine Tumors
NCT02246127	PHASE3	COMPLETED	Sequentiality of Everolimus and STZ-5FU in Advanced Pancreatic Neuroendocrine Tumor
NCT02588170	PHASE3	COMPLETED	Phase III Study of Surufatinib in Treating Advanced Extrapancreatic Neuroendocrine Tumors
NCT02589821	PHASE3	COMPLETED	Phase III Study of Surufatinib in Treating Advanced Pancreatic Neuroendocrine Tumors
NCT02840149	PHASE3	COMPLETED	SUV on 68Ga-DOTATATE PET/CT and Ki-67 Index in Neuro-Endocrine Tumors
NCT03042416	PHASE3	COMPLETED	18F-DOPA PET Imaging: an Evaluation of Biodistribution and Safety
NCT03136328	PHASE3	COMPLETED	Diagnosis and Staging of Neuroendocrine Tumors (NETs) Utilizing 68Ga-DOTATOC PET/CT Scan
NCT03590119	PHASE2/PHASE3	COMPLETED	Intra-arterial Lutetium-177-dotatate for Treatment of Patients With Neuro-endocrine Tumor Liver Metastases
NCT03673943	PHASE3	COMPLETED	Imaging of Patients With Known or Suspected Somatostatin Receptor Positive Neuroendocrine Tumors Using Cu64-DOTATATE
NCT04552847	PHASE2/PHASE3	COMPLETED	Al18F-NOTA-octreotide PET Imaging in Neuroendocrine Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LUTETIUM OXODOTREOTIDE LU-177	4	16
LANREOTIDE	4	15
EDOTREOTIDE GALLIUM GA-68	4	13
OCTREOTIDE	4	8
TELOTRISTAT ETHYL	4	8
CARBOPLATIN	4	7
SUNITINIB	4	5
CABOZANTINIB	4	4
PASIREOTIDE	4	4
COPPER OXODOTREOTIDE CU-64	4	3
EVEROLIMUS	4	2
FLUORODOPA F 18	4	2
FLUPHENAZINE DECANOATE	4	2
INDIUM IN 111 PENTETREOTIDE	4	2
IOBENGUANE I 131	4	2
LENVATINIB	4	2
LURBINECTEDIN	4	2
AXITINIB	4	1
BEVACIZUMAB	4	1
CABERGOLINE	4	1
DESIPRAMINE HYDROCHLORIDE	4	1
ENTRECTINIB	4	1
FUROSEMIDE	4	1
LEUCOVORIN	4	1
LITHIUM CARBONATE	4	1
NINTEDANIB	4	1
OXALIPLATIN	4	1
PACLITAXEL	4	1
PANOBINOSTAT	4	1
PAZOPANIB	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 4 predictive associations from 4 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
KDR Overexpression	Pazopanib	Sensitivity/Response	CIViC B	EID7854
MGMT Underexpression	Temozolomide	Sensitivity/Response	CIViC B	EID2904
SSTR5 Overexpression	Pasireotide	Sensitivity/Response	CIViC B	EID10193
MEN1 Loss-of-function	JQ1	Sensitivity/Response	CIViC D	EID9249