Endometrial cancer

Summary

Endometrial cancer (MONDO:0011962) is a cancer with 18 cohort genes (113 GWAS associations across 26 studies; 16 CIViC-evidence somatic drivers; 4 ClinVar predisposition records) and 1,019 clinical trials. The dominant Reactome pathway is Diseases of DNA repair (5 cohort genes). Molecularly, ERBB2 Amplification confers sensitivity to Trastuzumab in Endometrial Cancer (CIViC Level B); 15 further subtype–drug associations are mapped below. Top therapeutic interventions include letrozole, dostarlimab, and doxorubicin.

At a glance

• Classification: Cancer
• Cohort genes: 18
• GWAS associations: 113
• ClinVar variants: 4
• Clinical trials: 1,019
• Precision-medicine evidence (CIViC): 16 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	endometrial cancer
Mondo ID	MONDO:0011962
OMIM	608089
DOID	DOID:1380
ICD-10-CM	C54.1
NCIT	C27815
UMLS	C0007103
MedGen	2840
Anatomy (UBERON)	UBERON:0001295
Is cancer (heuristic)	yes

Also known as: cancer of endometrium · endometrial cancer · endometrial cancer, familial, autosomal dominant, somatic mutation · endometrial cancer, susceptibility to, autosomal dominant, somatic mutation · endometrial carcinoma, somatic · endometrial neoplasm · endometrium cancer · malignant endometrial neoplasm · malignant endometrium neoplasm · malignant neoplasm of endometrium · neoplasm of endometrium · tumor of endometrium · tumour of endometrium

Data availability: 4 ClinVar variants · 113 GWAS associations (26 studies).

Disease family

An umbrella term covering 2 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 › uterine cancer › endometrial cancer

Related subtypes (6): uterine adnexa cancer, placenta cancer, cervical cancer, uterine carcinoma, uterine corpus cancer, uterine carcinosarcoma

Subtypes (2): endometrial carcinoma, endometrioid stromal sarcoma

Genetics & variants

GWAS landscape

113 GWAS associations across 26 studies. Top hits map to 38 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs554833	3e-85	ABO	T
rs12682374	9e-29	PCAT1, CASC8, POU5F1B	?	0.93
rs1740828	9e-28	BOLA2P3 - CASC15	A	0.86
rs657152	4e-26	ABO	A
rs1219651	1e-25	FGFR2	?	1.09
rs11263763	2e-23	HNF1B	A	1.14
rs2981584	1e-21	FGFR2	?	0.94
rs10908278	3e-21	HNF1B	?	1.06
rs9600103	1e-19	RNY1P8 - MARK2P12	A	1.15
rs17601876	2e-18	MIR4713HG, CYP19A1	A	0.89
rs9300169	2e-18	SSPN-AS1, SSPN	?
rs112149573	2e-17	TOX3	?	1.08
rs2747716	4e-16	LINC02523, HEY2-AS1	A	1.11
rs78540526	1e-15	LINC01488 - PNCRNA-D	?	1.13
rs35409710	2e-15	HLA-DQB1	?	1.09
rs7463708	2e-15	PCAT1, PRNCR1, CASC19	?	1.08
rs9668810	3e-15	SSPN-AS1, SSPN	?
rs11651755	1e-14	HNF1B	?	1.06
rs7310615	6e-14	SH2B3	?
rs1485995	8e-14	LINC01488	?	0.95
rs143384	1e-13	GDF5	?
rs9273736	2e-13	HLA-DQB1	?	1.12
rs2976384	3e-13	PSCA, JRK	?	1.07
rs550057	4e-13	ABO	T
rs4733613	5e-13	LINC00824 - CCDC26	C	1.15
rs4135275	5e-13	PPARG	?
rs11856927	2e-12	CYP19A1, MIR4713HG	?	0.7
rs2585181	3e-12	PSCA - LY6K	?	1.05
rs998713	4e-12	SRP14-DT	A	0.91
rs1123573	5e-12	BCL11A	G

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90651054	Sato G	2023	43,098	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90308764	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651069	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90296493	Zhao X	2023	12,906	2,584,219	A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.
GCST90296494	Zhao X	2023	12,906	2,171,784	A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.
GCST90296495	Zhao X	2023	12,906	1,181,421	A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.
GCST90503275	Wilcox N	2025	1,974	225,419	The contribution of coding variants to the heritability of multiple cancer types using UK Biobank whole-exome sequencing data.
GCST90651044	Sato G	2023	1,892	183,466	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90079109	Backman JD	2021	1,536	39,469	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083095	Backman JD	2021	1,536	39,469	Exome sequencing and analysis of 454,787 UK Biobank participants.

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	2
Tier 4: intronic/intergenic	47

MAF distribution

Bucket	Variants
common (>=0.05)	49
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	33
intergenic_variant	9
non_coding_transcript_exon_variant	5
regulatory_region_variant	2
5_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs554833	9	133271745	T>A,C,G	0.05	intron_variant	ABO	3e-85	Tier 4: intronic/intergenic
rs12682374	8	127398703	C>A,G,T	0.05	intron_variant	PCAT1, CASC8, POU5F1B	9e-29	Tier 4: intronic/intergenic
rs1740828	6	21648854	G>A	0.47	intergenic_variant	BOLA2P3 - CASC15	9e-28	Tier 4: intronic/intergenic
rs657152	9	133263862	A>C,G,T	0.05	intron_variant	ABO	4e-26	Tier 4: intronic/intergenic
rs1219651	10	121584987	G>A,C,T	0.05	intron_variant	FGFR2	1e-25	Tier 4: intronic/intergenic
rs11263763	17	37743574	A>C,G	0.43	intron_variant	HNF1B	2e-23	Tier 4: intronic/intergenic
rs2981584	10	121590702	A>C,G,T	0.05	intron_variant	FGFR2	1e-21	Tier 4: intronic/intergenic
rs10908278	17	37739961	A>C,G,T	0.05	intron_variant	HNF1B	3e-21	Tier 4: intronic/intergenic
rs9600103	13	73237742	A>C,T	0.26	intergenic_variant	RNY1P8 - MARK2P12	1e-19	Tier 4: intronic/intergenic
rs17601876	15	51261712	A>C,G	0.5	intron_variant	MIR4713HG, CYP19A1	2e-18	Tier 4: intronic/intergenic
rs9300169	12	26273738	A>G	0.05	non_coding_transcript_exon_variant	SSPN-AS1, SSPN	2e-18	Tier 4: intronic/intergenic
rs112149573	16	52547333	G>C,T	0.05	intron_variant	TOX3	2e-17	Tier 4: intronic/intergenic
rs2747716	6	125687226	A>G,T	0.4	intron_variant	LINC02523, HEY2-AS1	4e-16	Tier 4: intronic/intergenic
rs78540526	11	69516650	C>T	0.05	regulatory_region_variant	LINC01488 - PNCRNA-D	1e-15	Tier 3: regulatory
rs35409710	6	32661126	G>A	0.05	intron_variant	HLA-DQB1	2e-15	Tier 4: intronic/intergenic
rs7463708	8	127091810	G>A,C,T	0.05	non_coding_transcript_exon_variant	PCAT1, PRNCR1, CASC19	2e-15	Tier 4: intronic/intergenic
rs9668810	12	26273487	T>C	0.05	non_coding_transcript_exon_variant	SSPN-AS1, SSPN	3e-15	Tier 4: intronic/intergenic
rs11651755	17	37739849	T>C	0.05	intron_variant	HNF1B	1e-14	Tier 4: intronic/intergenic
rs7310615	12	111427245	C>A,G,T	0.05	intron_variant	SH2B3	6e-14	Tier 4: intronic/intergenic
rs1485995	11	69492939	G>A,C	0.05	non_coding_transcript_exon_variant	LINC01488	8e-14	Tier 4: intronic/intergenic
rs143384	20	35437976	G>A,C,T	0.05	5_prime_UTR_variant	GDF5	1e-13	Tier 2: splice/UTR
rs9273736	6	32661595	G>A,C	0.05	intron_variant	HLA-DQB1	2e-13	Tier 4: intronic/intergenic
rs2976384	8	142671576	T>A,C	0.05	intergenic_variant	PSCA, JRK	3e-13	Tier 4: intronic/intergenic
rs550057	9	133271182	T>A,C	0.05	intron_variant	ABO	4e-13	Tier 4: intronic/intergenic
rs4733613	8	128587032	C>A,G,T	0.14	intergenic_variant	LINC00824 - CCDC26	5e-13	Tier 4: intronic/intergenic
rs4135275	3	12402345	A>G	0.05	intron_variant	PPARG	5e-13	Tier 4: intronic/intergenic
rs11856927	15	51256508	G>T	0.05	intron_variant	CYP19A1, MIR4713HG	2e-12	Tier 4: intronic/intergenic
rs2585181	8	142690296	C>A	0.05	intergenic_variant	PSCA - LY6K	3e-12	Tier 4: intronic/intergenic
rs998713	15	40086266	A>C,G,T	0.39	intron_variant	SRP14-DT	4e-12	Tier 4: intronic/intergenic
rs1123573	2	60480453	A>G	0.05	intron_variant	BCL11A	5e-12	Tier 4: intronic/intergenic

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
5294	NM_001048174.2(MUTYH):c.1103G>A (p.Gly368Asp)	MUTYH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4538530	NM_000179.3(MSH6):c.3673A>T (p.Thr1225Ser)	MSH6	Likely pathogenic	criteria provided, single submitter
5563	NM_001040108.2(MLH3):c.885del (p.His296fs)	MLH3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2834667	NM_000059.4(BRCA2):c.9541A>T (p.Met3181Leu)	BRCA2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 125 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
MSH6			CIViC #2478
RIT1			CIViC #4875
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
ANTXR1	LoF	LUNG,MEL,STAD,UTUC	CIViC #524
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
FGFR2	Act	BRCA,CHOL,LUSC,SACA,UCEC	CIViC #22
KIT	Act	AML,GIST,MEL,MGCT	CIViC #29
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
MLH1			CIViC #3532
MRE11			CIViC #3586
MSH2			CIViC #3628
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37
PMS2	ambiguous	HCC	CIViC #4371
POLE	Act	ACC,BLCA	CIViC #4386
PTEN	LoF	ANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTC	CIViC #41
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MSH6	Orphanet:144	Lynch syndrome
MSH6	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
RIT1	Orphanet:648	Noonan syndrome
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
ANTXR1	Orphanet:2067	GAPO syndrome
ERBB2	Orphanet:213726	Serous carcinoma of the corpus uteri
ERBB2	Orphanet:2800	Extramammary Paget disease
ERBB2	Orphanet:388	Hirschsprung disease
ERBB2	Orphanet:99976	Adenocarcinoma of the oesophagus and oesophagogastric junction
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3
KIT	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
KIT	Orphanet:158766	Typical urticaria pigmentosa
KIT	Orphanet:158769	Plaque-form urticaria pigmentosa
KIT	Orphanet:158772	Nodular urticaria pigmentosa
KIT	Orphanet:158775	Smoldering systemic mastocytosis
KIT	Orphanet:158778	Isolated bone marrow mastocytosis
KIT	Orphanet:280785	Bullous diffuse cutaneous mastocytosis
KIT	Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis
KIT	Orphanet:2884	Piebaldism
KIT	Orphanet:44890	Gastrointestinal stromal tumor

Cohort genes → proteins

18 cohort genes, 18 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	14
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	clinvar,civic_evidence
RIT1	HGNC:10023	ENSG00000143622	Q92963	GTP-binding protein Rit1	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
ANTXR1	HGNC:21014	ENSG00000169604	Q9H6X2	Anthrax toxin receptor 1	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	civic_evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	civic_evidence
MRE11	HGNC:7230	ENSG00000020922	P49959	Double-strand break repair protein MRE11	civic_evidence
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	civic_evidence
POLE	HGNC:9177	ENSG00000177084	Q07864	DNA polymerase epsilon catalytic subunit A	civic_evidence
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
MLH3	HGNC:7128	ENSG00000119684	Q9UHC1	DNA mismatch repair protein Mlh3	clinvar
MUTYH	HGNC:7527	ENSG00000132781	Q9UIF7	Adenine DNA glycosylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).
RIT1	GTP-binding protein Rit1	Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
ANTXR1	Anthrax toxin receptor 1	Plays a role in cell attachment and migration.
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
MRE11	Double-strand break repair protein MRE11	Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
POLE	DNA polymerase epsilon catalytic subunit A	Catalytic component of the DNA polymerase epsilon complex.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
MLH3	DNA mismatch repair protein Mlh3	Probably involved in the repair of mismatches in DNA.
MUTYH	Adenine DNA glycosylase	Involved in oxidative DNA damage repair.

Protein-family classification

Druggable: 6 · Difficult: 2 · Unknown: 10 · Druggable fraction: 0.33

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
Kinase	4	6.2×	0.017
Phosphatase	1	4.7×	0.486
Other/Unknown	10	1.0×	0.792
Transcription factor	2	0.9×	0.792
Enzyme (other)	1	0.7×	0.792

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N
RIT1	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
ANTXR1	Other/Unknown	no		VWF_A, Anthrax_toxin_rcpt_C, Anthrax_toxin_rcpt_extracel
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MRE11	Other/Unknown	no		Mre11, Calcineurin-like_PHP, Mre11_DNA-bd
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
POLE	Transcription factor	no	2.7.7.7	DNA-dir_DNA_pol_B_exonuc, DNA-dir_DNA_pol_B, RNaseH-like_sf
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
MLH3	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MUTYH	Other/Unknown	no		NUDIX_hydrolase_dom, HhH_motif, HhH-GPD_domain

Expression context

Cohort genes with no expression data: 0.

18 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)	18
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	4
secondary oocyte	4
oocyte	3
calcaneal tendon	3
ganglionic eminence	2
leukocyte	2
monocyte	2
mononuclear cell	2
male germ line stem cell (sensu Vertebrata) in testis	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
embryo	1
tendon of biceps brachii	1
decidua	1
palpebral conjunctiva	1
stromal cell of endometrium	1
lower esophagus mucosa	1
right uterine tube	1
sural nerve	1
C1 segment of cervical spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
RIT1	268	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
ANTXR1	270	ubiquitous	marker	stromal cell of endometrium, decidua, palpebral conjunctiva
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
MLH1	296	ubiquitous	marker	tibialis anterior, skeletal muscle tissue of rectus abdominis, deltoid
MRE11	254	ubiquitous	marker	calcaneal tendon, oocyte, secondary oocyte
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
POLE	221	ubiquitous	marker	right hemisphere of cerebellum, right testis, cerebellar hemisphere
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
MLH3	270	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
MUTYH	134	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 32.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
KRAS	14,509
PTEN	11,626
ERBB2	9,659
KIT	6,087
PIK3CA	5,157
BRCA2	4,839
MSH2	4,537
MLH1	4,435
MSH6	4,091

Intra-cohort edges

A	B	Sources
BRCA2	MLH1	string_interaction
BRCA2	MRE11	string_interaction
BRCA2	MSH2	string_interaction
BRCA2	MSH6	string_interaction
BRCA2	PMS2	string_interaction
BRCA2	TP53	string_interaction
ERBB2	KRAS	string_interaction
ERBB2	PIK3CA	string_interaction
KIT	PIK3CA	biogrid_interaction
KIT	TP53	biogrid_interaction
KRAS	PIK3CA	string_interaction
KRAS	PTEN	string_interaction
KRAS	TP53	string_interaction
MLH1	MLH3	biogrid_interaction, intact
MLH1	MSH2	string_interaction
MLH1	MSH6	string_interaction
MLH1	MUTYH	string_interaction
MLH1	PMS2	biogrid_interaction, intact, string_interaction
MLH1	POLE	string_interaction
MRE11	PMS2	string_interaction
MSH2	MSH6	biogrid_interaction, intact, string_interaction
MSH2	MUTYH	intact, string_interaction
MSH2	PMS2	string_interaction
MSH2	POLE	string_interaction
MSH6	MUTYH	string_interaction
MSH6	PMS2	string_interaction
MSH6	POLE	biogrid_interaction, string_interaction
MUTYH	PMS2	string_interaction
MUTYH	POLE	string_interaction
PIK3CA	PTEN	string_interaction
PMS2	POLE	string_interaction
PTEN	TP53	string_interaction

Structural data

PDB: 17 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
PIK3CA	P42336	135
ERBB2	P04626	63
FGFR2	P21802	63
KIT	P10721	52
MSH2	P43246	30
POLE	Q07864	18
BRCA2	P51587	14
PTEN	P60484	12
MRE11	P49959	10
PMS2	P54278	9
MSH6	P52701	8
MLH1	P40692	7
ANTXR1	Q9H6X2	5
RIT1	Q92963	3
MUTYH	Q9UIF7	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MLH3	Q9UHC1	56.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 291. Enrichment computed across 18 evidence-associated genes (18 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 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Diseases of DNA repair	5	158.6×	2e-08	MSH6, BRCA2, MLH1, MRE11, MSH2
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	4	181.3×	6e-07	MSH6, MLH1, MSH2, PMS2
Mismatch Repair	3	475.8×	1e-06	MSH6, MLH1, MSH2
Diseases of Mismatch Repair (MMR)	3	475.8×	1e-06	MSH6, MLH1, MSH2
Meiosis	4	63.4×	2e-05	BRCA2, MLH1, MLH3, MRE11
DNA Repair	5	27.4×	4e-05	MSH6, BRCA2, MLH1, MRE11, MSH2
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	3	135.9×	5e-05	MLH1, MSH2, PMS2
Defective Mismatch Repair Associated With MLH1	2	634.4×	5e-05	MLH1, PMS2
Defective Mismatch Repair Associated With MSH6	2	634.4×	5e-05	MSH6, MSH2
Defective Mismatch Repair Associated With PMS2	2	634.4×	5e-05	MLH1, PMS2
Signaling by ERBB2 ECD mutants	3	112.0×	5e-05	ERBB2, KRAS, PIK3CA
Reproduction	4	42.3×	5e-05	BRCA2, MLH1, MLH3, MRE11
TP53 Regulates Transcription of DNA Repair Genes	4	40.3×	5e-05	TP53, MLH1, MSH2, PMS2
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	3	86.5×	1e-04	KIT, KRAS, PIK3CA
Defective Mismatch Repair Associated With MSH2	2	423.0×	1e-04	MSH6, MSH2
RAF/MAP kinase cascade	5	17.0×	1e-04	ERBB2, FGFR2, KIT, KRAS, PIK3CA
Signaling by ERBB2 KD Mutants	3	70.5×	2e-04	ERBB2, KRAS, PIK3CA
Meiotic recombination	4	28.8×	2e-04	BRCA2, MLH1, MLH3, MRE11
Constitutive Signaling by Aberrant PI3K in Cancer	4	28.2×	2e-04	ERBB2, FGFR2, KIT, PIK3CA
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	4	21.5×	4e-04	ERBB2, FGFR2, KIT, PIK3CA
Signaling by FGFR2 in disease	3	44.3×	5e-04	FGFR2, KRAS, PIK3CA
Signaling by SCF-KIT	3	41.4×	6e-04	KIT, KRAS, PIK3CA
HDR through Homologous Recombination (HRR)	3	31.7×	0.001	BRCA2, MRE11, POLE
PIP3 activates AKT signaling	4	14.8×	0.002	ERBB2, FGFR2, KIT, PIK3CA
Signaling by FGFR4 in disease	2	105.7×	0.002	KRAS, PIK3CA
Constitutive Signaling by Overexpressed ERBB2	2	105.7×	0.002	ERBB2, KRAS
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2	105.7×	0.002	BRCA2, MRE11
HDR through MMEJ (alt-NHEJ)	2	97.6×	0.002	BRCA2, MRE11
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	2	97.6×	0.002	KRAS, PIK3CA
Signaling by PDGFRA extracellular domain mutants	2	97.6×	0.002	KRAS, PIK3CA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mismatch repair	6	216.1×	7e-11	MSH6, MLH1, MLH3, MSH2, MUTYH, PMS2
somatic hypermutation of immunoglobulin genes	4	234.1×	4e-07	MSH6, MLH1, MSH2, PMS2
somatic recombination of immunoglobulin gene segments	3	702.2×	7e-07	MSH6, MSH2, PMS2
positive regulation of isotype switching to IgA isotypes	3	468.1×	3e-06	MLH1, MSH2, PMS2
positive regulation of isotype switching to IgG isotypes	3	255.3×	2e-05	MLH1, MSH2, PMS2
response to X-ray	3	147.8×	8e-05	BRCA2, TP53, MSH2
isotype switching	3	140.4×	8e-05	MSH6, MLH1, MSH2
double-strand break repair	4	45.1×	1e-04	BRCA2, TP53, MRE11, MSH2
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	3	82.6×	3e-04	BRCA2, TP53, MSH2
embryonic organ development	3	80.2×	3e-04	TP53, FGFR2, POLE
determination of adult lifespan	3	72.0×	4e-04	MSH6, TP53, MSH2
actin cytoskeleton organization	4	17.6×	0.003	ANTXR1, KIT, KRAS, PIK3CA
positive regulation of cellular senescence	2	144.0×	0.003	TP53, KRAS
phosphatidylinositol 3-kinase/protein kinase B signal transduction	3	35.1×	0.003	ERBB2, PIK3CA, PTEN
Ras protein signal transduction	3	34.2×	0.003	RIT1, TP53, KRAS
negative regulation of DNA recombination	2	124.8×	0.004	MSH6, MSH2
DNA repair	4	14.2×	0.005	MSH6, MRE11, MSH2, MUTYH
mitotic intra-S DNA damage checkpoint signaling	2	104.0×	0.005	MRE11, MSH2
glial cell proliferation	2	98.5×	0.005	TP53, KRAS
homologous chromosome pairing at meiosis	2	66.9×	0.010	MLH1, MRE11
response to gamma radiation	2	64.6×	0.010	BRCA2, TP53
regulation of ERK1 and ERK2 cascade	2	64.6×	0.010	ERBB2, FGFR2
reciprocal meiotic recombination	2	62.4×	0.010	MLH3, MRE11
digestive tract development	2	58.5×	0.011	FGFR2, KIT
negative regulation of neuron apoptotic process	3	18.5×	0.011	KRAS, MSH2, PIK3CA
meiotic mismatch repair	1	936.2×	0.012	MSH6
somatic recombination of immunoglobulin genes involved in immune response	1	936.2×	0.012	MSH2
response to muscle inactivity	1	936.2×	0.012	PIK3CA
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	936.2×	0.012	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	936.2×	0.012	FGFR2

Therapeutics

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 7 · Undrugged: 11

Druggability breadth: 13 of 18 evidence-associated genes (72%) 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
TP53	NITROFURANTOIN
ERBB2	CLOTRIMAZOLE
FGFR2	PONATINIB
KIT	PONATINIB
KRAS	VEMURAFENIB
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
KIT	99	4
ERBB2	83	4
PIK3CA	67	4
FGFR2	59	4
KRAS	11	4
MSH6	1	2
RIT1	0	0
ANTXR1	0	0
MLH1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
FGFR2	966	Binding:940, Functional:22, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
MRE11	36	Binding:36
MSH6	10	Binding:10
MSH2	9	Binding:9
PTEN	8	Binding:8
PMS2	1	Binding:1
MUTYH	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
KIT	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
POLE	2.7.7.7	DNA-directed DNA polymerase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869
ERBB2	1,221
FGFR2	966
KIT	2,305
KRAS	861
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 18; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ERBB2, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	TP53, ERBB2, FGFR2, KIT, KRAS, PIK3CA
B	Phased (≥1) drug, not yet approved	1	MSH6
C	Druggable family + PDB, no drug	1	PTEN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	10	RIT1, ANTXR1, MLH1, MRE11, MSH2, PMS2, POLE, BRCA2, MLH3, MUTYH

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MLH1	0	MSH6
PMS2	1	MSH6
POLE	0	MSH6
PTEN	8	TP53
MUTYH	1	MSH6
RIT1	0	—
ANTXR1	0	—
MRE11	36	—
MSH2	9	—
BRCA2	0	—
MLH3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,019.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	496
PHASE2	220
PHASE1	125
PHASE1/PHASE2	75
PHASE3	62
EARLY_PHASE1	20
PHASE2/PHASE3	11
PHASE4	10

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02543710	PHASE4	RECRUITING	Biomarker Guided Treatment in Gynaecological Cancer
NCT06726291	PHASE4	RECRUITING	Akynzeo as Antiemetic Treatment in Patients With Endometrial Cancer
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT07462663	PHASE4	NOT_YET_RECRUITING	SHAPE-ENDO: Multimodal Pre-Surgical Optimization in Patients With Obesity and Early-Stage Endometrial Cancer (Phase 1)
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00719017	PHASE4	UNKNOWN	Upper Vaginectomy Versus Brachytherapy in Patients With Early Stage Endometrial Cancer Treated With Laparoscopic Surgery
NCT03349463	PHASE4	UNKNOWN	Evaluation of Fluciclovine Uptake in Patients With Cervical, Ovarian Epithelial or Endometrial Cancers.
NCT03752606	PHASE4	COMPLETED	Application of Tachosil During Lymphadenectomy
NCT05651282	PHASE4	COMPLETED	Risk Evaluation and Screening to Tailor Prevention and Reduce the Incidence of Endometrial Cancer
NCT06049693	PHASE4	COMPLETED	Iron Prehabilitation in Endometrial Cancer
NCT01820858	PHASE3	ACTIVE_NOT_RECRUITING	The Efficacy and Safety of the Postoperative Adjuvant Treatment in Patients With High-risk Stage I Endometrial Carcinoma
NCT03463252	PHASE2/PHASE3	RECRUITING	Value of LNG-IUS as Fertility-preserving Treatment of EAH and EC
NCT03469674	PHASE3	ACTIVE_NOT_RECRUITING	PORTEC-4a: Molecular Profile-based Versus Standard Adjuvant Radiotherapy in Endometrial Cancer
NCT03785288	PHASE3	RECRUITING	Vaginal Cuff Brachytherapy Fractionation Study
NCT04073706	PHASE3	RECRUITING	Sentinel Node Biopsy in Endometrial Cancer
NCT04269200	PHASE3	ACTIVE_NOT_RECRUITING	Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer
NCT04634877	PHASE3	ACTIVE_NOT_RECRUITING	Study of Pembrolizumab (MK-3475) in Combination With Adjuvant Chemotherapy With or Without Radiotherapy in Participants With Newly Diagnosed Endometrial Cancer After Surgery With Curative Intent (MK-3475-B21 / KEYNOTE-B21 / ENGOT-en11 / GOG-3053)
NCT04789694	PHASE3	RECRUITING	Prehabilitation in Gynaecological Cancer Patients
NCT05077215	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of a Repurposed Drug Added to the Combination of Len Plus Pem in Advanced Endometrial Cancer
NCT05173987	PHASE3	ACTIVE_NOT_RECRUITING	Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma (MK-3475-C93/KEYNOTE-C93/GOG-3064/ENGOT-en15)
NCT05201547	PHASE3	ACTIVE_NOT_RECRUITING	Endometrial Cancer Patientes MMR Deficient Comparing Chemotherapy vs Dostarlimab in First Line
NCT05255653	PHASE2/PHASE3	RECRUITING	Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features
NCT05316935	PHASE2/PHASE3	RECRUITING	GnRHa + Letrozole in Non-obese Progestin-insensitive Endometrial Cancer and Atypical Hyperplasia Patients
NCT05489848	PHASE2/PHASE3	NOT_YET_RECRUITING	Chemotherapy vs Chemoradiotherapy for Post-operative Endometrial Cancer Patients With P53-mutation
NCT05524389	PHASE3	NOT_YET_RECRUITING	Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions
NCT05611931	PHASE3	ACTIVE_NOT_RECRUITING	Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma
NCT05770102	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 02: Atezolizumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With High Tumour Mutational Burden (TMB) or Microsatellite Instability-high (MSI-high) or Proven Constitutional Mismatch Repair Deficiency (CMMRD) Disposition
NCT05797831	PHASE2/PHASE3	RECRUITING	Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer
NCT06132958	PHASE3	ACTIVE_NOT_RECRUITING	Sacituzumab Tirumotecan (MK-2870) in Post Platinum and Post Immunotherapy Endometrial Cancer (MK-2870-005)
NCT06340568	PHASE3	RECRUITING	A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine Cancer
NCT06379113	PHASE2/PHASE3	RECRUITING	GnRHa + Letrozole in Obese Progestin-insensitive Endometrial Cancer Patients
NCT06475599	PHASE3	NOT_YET_RECRUITING	Anlotinib Hydrochloride Capsules Combined With TQB2450 in the Treatment of Endometrial Cancer
NCT06486441	PHASE3	ACTIVE_NOT_RECRUITING	Study of Sacituzumab Govitecan Versus Treatment of Physician’s Choice in Participants With Endometrial Cancer After Platinum-Based Chemotherapy and Immunotherapy (ASCENT-GYN-01/GOG-3104/ENGOT-en26)
NCT06584032	PHASE3	RECRUITING	Study of Fruquintinib Plus Sintilimab for Treatment of Advanced Endometrial Cancer
NCT06712472	PHASE3	RECRUITING	Randomized Phase III Trial Testing Maintenance Olaparib Versus Observation After Adjuvant Chemoradiation for p53abn Endometrial Cancer
NCT06851663	PHASE2/PHASE3	RECRUITING	Trop2-targeted immunoPET Imaging of Solid Tumors
NCT06952504	PHASE3	RECRUITING	A Study to Compare Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone as Treatment in Participants With Mismatch Repair Proficient Endometrial Cancer (MK-2870-033/TroFuse-033/GOG-3119/ENGOT-en29)
NCT06989112	PHASE3	RECRUITING	DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC 3+/2+), Mismatch Repair Proficient (pMMR) Endometrial Cancer
NCT07022483	PHASE3	RECRUITING	Study of Trastuzumab Deruxtecan Versus Standard of Care Chemotherapy for HER2-Expressing (IHC 3+/2+) Endometrial Cancer
NCT07044336	PHASE3	RECRUITING	Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LETROZOLE	4	15
DOSTARLIMAB	4	11
DOXORUBICIN	4	8
GEMCITABINE	4	8
MEGESTROL ACETATE	4	8
MEDROXYPROGESTERONE ACETATE	4	7
LENVATINIB	4	6
INDOCYANINE GREEN ACID FORM	4	5
ABEMACICLIB	4	4
FILGRASTIM	4	4
OLAPARIB	4	4
RUCAPARIB	4	4
FRUQUINTINIB	4	3
MIRVETUXIMAB SORAVTANSINE	4	3
NIRAPARIB	4	3
PACLITAXEL	4	3
AMIFOSTINE	4	2
AVELUMAB	4	2
AXITINIB	4	2
CEMIPLIMAB	4	2
CISPLATIN	4	2
DIPHENHYDRAMINE	4	2
DURVALUMAB	4	2
GONADORELIN ACETATE	4	2
IFOSFAMIDE	4	2
INAVOLISIB	4	2
LEVONORGESTREL	4	2
LURBINECTEDIN	4	2
PEMBROLIZUMAB	4	2
PEMIGATINIB	4	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 16 predictive associations from 17 curated evidence items; also 8 oncogenic, 4 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
ERBB2 Amplification	Trastuzumab	Sensitivity/Response	CIViC B	EID1098
FGFR2 Mutation	Dovitinib + Fulvestrant	Sensitivity/Response	CIViC B	EID6457
KRAS Mutation	Ridaforolimus + Temsirolimus	Sensitivity/Response	CIViC B	EID894
MSI High	Carboplatin + Dostarlimab + Paclitaxel	Sensitivity/Response	CIViC B	EID12341
MSI High	Paclitaxel + Dostarlimab + Carboplatin	Sensitivity/Response	CIViC B	EID12343
PIK3CA Mutation	Temsirolimus + Ridaforolimus	Sensitivity/Response	CIViC B	EID892
PTEN Loss	Temsirolimus + Ridaforolimus	Resistance	CIViC B	EID893
KIT EXPRESSION	Imatinib	Sensitivity/Response	CIViC C	EID1024 +1
AKT1 L52R	Capivasertib	Sensitivity/Response	CIViC C	EID10762
FGFR2::BICC1 Fusion	Erdafitinib	Sensitivity/Response	CIViC C	EID1920
POLE Mutation	Pembrolizumab	Sensitivity/Response	CIViC C	EID1862
FGFR2 Mutation	Ponatinib	Sensitivity/Response	CIViC D	EID1236
FGFR2 N550K	PD173074	Sensitivity/Response	CIViC D	EID1322
MRE11 Loss	Talazoparib	Sensitivity/Response	CIViC D	EID876
PIK3CA Mutation	Pictilisib	Sensitivity/Response	CIViC D	EID1616
PTEN Loss	Temsirolimus	Sensitivity/Response	CIViC D	EID1614