Endometrioid adenocarcinoma

Summary

Endometrioid adenocarcinoma (MONDO:0005026) is a disease (an umbrella term covering 6 Mondo subtypes) with 1 cohort gene and 18 clinical trials. Top therapeutic interventions include cabozantinib, capivasertib, and copanlisib.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	endometrioid adenocarcinoma
Mondo ID	MONDO:0005026
EFO	EFO:0000466
NCIT	C3769
UMLS	C1569637
MedGen	293976
Is cancer (heuristic)	no

Also known as: endometrioid adenocarcinoma · endometrioid carcinoma · endometrioid carcinoma of female reproductive system · endometrioid carcinoma of the female reproductive system · female reproductive endometrioid carcinoma

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › reproductive system cancer › female reproductive organ cancer › endometrioid adenocarcinoma

Related subtypes (8): vaginal cancer, vulva cancer, fallopian tube cancer, uterine cancer, adenocarcinofibroma, adenosarcoma, ovarian cancer, gestational choriocarcinoma

Subtypes (6): cervical endometrioid adenocarcinoma, fallopian tube endometrioid adenocarcinoma, stage I endometrioid carcinoma, stage II endometrioid carcinoma, endometrial endometrioid adenocarcinoma, ovarian endometrioid adenocarcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
376500	NM_006231.4(POLE):c.857C>G (p.Pro286Arg)	POLE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POLE	Orphanet:352712	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome
POLE	Orphanet:440437	Familial colorectal cancer Type X
POLE	Orphanet:447877	Polymerase proofreading-related polyposis
POLE	Orphanet:85173	IMAGe syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
POLE	HGNC:9177	ENSG00000177084	Q07864	DNA polymerase epsilon catalytic subunit A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POLE	DNA polymerase epsilon catalytic subunit A	Catalytic component of the DNA polymerase epsilon complex.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POLE	Transcription factor	no	2.7.7.7	DNA-dir_DNA_pol_B_exonuc, DNA-dir_DNA_pol_B, RNaseH-like_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	1
right hemisphere of cerebellum	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POLE	221	ubiquitous	marker	right hemisphere of cerebellum, right testis, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POLE	3,267

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POLE	Q07864	18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
DNA replication initiation	1	1427.5×	0.005	POLE
PCNA-Dependent Long Patch Base Excision Repair	1	519.1×	0.005	POLE
Gap-filling DNA repair synthesis and ligation in GG-NER	1	439.2×	0.005	POLE
Recognition of DNA damage by PCNA-containing replication complex	1	380.7×	0.005	POLE
Termination of translesion DNA synthesis	1	346.1×	0.005	POLE
Activation of the pre-replicative complex	1	326.3×	0.005	POLE
Dual Incision in GG-NER	1	259.6×	0.006	POLE
HDR through Homologous Recombination (HRR)	1	190.3×	0.006	POLE
Gap-filling DNA repair synthesis and ligation in TC-NER	1	178.4×	0.006	POLE
Dual incision in TC-NER	1	173.0×	0.006	POLE

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
DNA replication proofreading	1	5617.3×	0.001	POLE
leading strand elongation	1	4213.0×	0.001	POLE
nucleotide-excision repair, DNA gap filling	1	2808.7×	0.001	POLE
base-excision repair, gap-filling	1	1123.5×	0.002	POLE
DNA synthesis involved in DNA repair	1	936.2×	0.002	POLE
DNA-templated DNA replication	1	561.7×	0.003	POLE
embryonic organ development	1	481.5×	0.003	POLE
G1/S transition of mitotic cell cycle	1	200.6×	0.006	POLE
DNA replication	1	165.2×	0.007	POLE
mitotic cell cycle	1	133.8×	0.007	POLE

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Belinostat, Bevacizumab, Carboplatin, Paclitaxel, Sargramostim, Temsirolimus.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
POLE	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POLE	2.7.7.7	DNA-directed DNA polymerase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

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

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

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
POLE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 18.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	7
PHASE1	5
Not specified	4
PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02598219	PHASE3	ACTIVE_NOT_RECRUITING	Evaluation of Sentinel Node Policy in Early Stage Endometrial Carcinomas at Intermediate and High Risk of Recurrence.
NCT02834013	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
NCT03660826	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Combination of Olaparib and Durvalumab, Cediranib and Durvalumab, Olaparib and Capivasertib, and Cediranib Alone in Recurrent or Refractory Endometrial Cancer Following the Earlier Phase of the Study That Tested Olaparib and Cediranib in Comparison to Cediranib Alone, and Olaparib Alone
NCT05080556	PHASE2	RECRUITING	Adaptive ChemoTherapy for Ovarian Cancer in Patients With Replased Platinum-sensitive High Grade Serous or High Grade Endometrioid Ovarian Cancer
NCT05112601	PHASE2	RECRUITING	Testing Nivolumab With or Without Ipilimumab in Deficient Mismatch Repair System (dMMR) Recurrent Endometrial Carcinoma
NCT01935934	PHASE2	COMPLETED	Cabozantinib S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer
NCT02728258	PHASE2	COMPLETED	Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer
NCT03824704	PHASE2	TERMINATED	A Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)
NCT05001282	PHASE1/PHASE2	TERMINATED	A Study to Evaluate ELU001 in Patients With Solid Tumors That Overexpress Folate Receptor Alpha (FRα)
NCT03875820	PHASE1	ACTIVE_NOT_RECRUITING	Phase I Trial of Defactinib and VS-6766.
NCT01440998	PHASE1	COMPLETED	Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer
NCT03345784	PHASE1	TERMINATED	Testing AZD1775 inC Combination With Radiotherapy and Chemotherapy in Cervical, Upper Vaginal and Uterine Cancers
NCT03748186	PHASE1	COMPLETED	Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody Drug Conjugate in Ovarian & Endometrial Cancers
NCT04498520	PHASE1	WITHDRAWN	Abexinostat, Palbociclib, and Fulvestrant for the Treatment of Breast or Gynecologic Cancer
NCT04291612	Not specified	RECRUITING	Observational Study of Women With Endometrial Cancer Who Receive the Standard Treatment for Their Disease
NCT06549855	Not specified	NOT_YET_RECRUITING	PD-1 Inhibitor Combined With Progesterone Treatment in FST for Patients With MMRd Endometrial Cancer
NCT01732432	Not specified	WITHDRAWN	Endometriosis and Frequency of Endometriosis-associated Ovarian Carcinomas (EAOC)
NCT04458597	Not specified	COMPLETED	Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CABOZANTINIB	4	3
CAPIVASERTIB	4	1
COPANLISIB	4	1
MEGESTROL ACETATE	4	1
RUCAPARIB	4	1
ABEXINOSTAT	3	1
AVUTOMETINIB	3	1
CEDIRANIB MALEATE	3	1
DEFACTINIB	3	1
ADAVOSERTIB	2	1
LUVELTAMAB TAZEVIBULIN	2	1
PASIFOLATE EXATECAN	1	1
CHEMBL4862042	0	1
CHEMBL4071215	0	1