Female reproductive organ cancer

Summary

Female reproductive organ cancer (MONDO:0001416) is a cancer (an umbrella term covering 9 Mondo subtypes) with 1 cohort gene (1 GWAS associations across 8 studies; 1 CIViC-evidence somatic driver) and 396 clinical trials. Top therapeutic interventions include prochlorperazine, hydromorphone, and indocyanine green acid form.

At a glance

• Classification: Cancer
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 1
• Clinical trials: 396

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	female reproductive organ cancer
Mondo ID	MONDO:0001416
EFO	EFO:1001331
DOID	DOID:120
ICD-10-CM	C51-C58
NCIT	C4913
SNOMED CT	126907002
UMLS	C0699889
MedGen	195944
Anatomy (UBERON)	UBERON:0003134
Is cancer (heuristic)	yes

Also known as: cancer of female reproductive organ · female reproductive cancer · female reproductive organ cancer · gynecologic cancer · malignant female reproductive organ neoplasm · malignant female reproductive system neoplasm · malignant female reproductive system tumor · malignant female reproductive system tumour · malignant gynecologic neoplasm · malignant gynecologic tumor · malignant gynecologic tumour · malignant neoplasm of female reproductive organ · malignant neoplasm of female reproductive system · malignant neoplasm of the female reproductive system · malignant tumor of female reproductive system · malignant tumor of the female reproductive system · malignant tumour of female reproductive system · malignant tumour of the female reproductive system

Data availability: 1 GWAS association (8 studies).

Disease family

An umbrella term covering 9 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

Related subtypes (7): malignant Leydig cell tumor, malignant Sertoli cell tumor, prepuce cancer, pituitary cancer, male reproductive organ cancer, gonadoblastoma, Buschke Lowenstein tumor

Subtypes (9): vaginal cancer, vulva cancer, fallopian tube cancer, uterine cancer, adenocarcinofibroma, endometrioid adenocarcinoma, adenosarcoma, ovarian cancer, gestational choriocarcinoma

Genetics & variants

GWAS landscape

1 GWAS associations across 8 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs3734620	2e-08	KCNK16	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90435609	Zhou W	2018	2,463	389,695	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90651511	Liu TY	2025	955	112,967	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90481508	Verma A	2024	558	32,013	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90041851	Jiang L	2021	316	247,224	A generalized linear mixed model association tool for biobank-scale data.
GCST90435612	Zhou W	2018	306	389,695	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90435670	Zhou W	2018	220	380,016	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90042877	Jiang L	2021	171	247,369	A generalized linear mixed model association tool for biobank-scale data.
GCST90041852	Jiang L	2021	138	247,402	A generalized linear mixed model association tool for biobank-scale data.

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	0

MAF distribution

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

Functional consequences

Consequence	Count
5_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs3734620	6	39322661	G>A		5_prime_UTR_variant	KCNK16	2e-08	Tier 2: splice/UTR

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
PAX8			CIViC #75

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PAX8	Orphanet:146	Differentiated thyroid carcinoma
PAX8	Orphanet:95712	Thyroid ectopia
PAX8	Orphanet:95713	Athyreosis
PAX8	Orphanet:95720	Thyroid hypoplasia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PAX8	HGNC:8622	ENSG00000125618	Q06710	Paired box protein Pax-8	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAX8	Paired box protein Pax-8	Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells.

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)
PAX8	Transcription factor	no		Paired_dom, Homeodomain-like_sf, Pax2_C

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
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAX8	242	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX8	1,994

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PAX8	Q06710	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Formation of intermediate mesoderm	1	1427.5×	0.001	PAX8
Formation of the nephric duct	1	634.4×	0.002	PAX8

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
regulation of thyroid-stimulating hormone secretion	1	16852.0×	6e-04	PAX8
pronephric field specification	1	8426.0×	6e-04	PAX8
metanephric comma-shaped body morphogenesis	1	8426.0×	6e-04	PAX8
obsolete negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis	1	8426.0×	6e-04	PAX8
obsolete negative regulation of apoptotic process involved in metanephric collecting duct development	1	8426.0×	6e-04	PAX8
obsolete negative regulation of apoptotic process involved in metanephric nephron tubule development	1	8426.0×	6e-04	PAX8
positive regulation of metanephric DCT cell differentiation	1	8426.0×	6e-04	PAX8
negative regulation of mesenchymal cell apoptotic process involved in metanephros development	1	5617.3×	8e-04	PAX8
metanephric distal convoluted tubule development	1	4213.0×	8e-04	PAX8
metanephric S-shaped body morphogenesis	1	4213.0×	8e-04	PAX8
positive regulation of thyroid hormone generation	1	4213.0×	8e-04	PAX8
metanephric epithelium development	1	3370.4×	8e-04	PAX8
metanephric nephron tubule formation	1	3370.4×	8e-04	PAX8
regulation of metanephric nephron tubule epithelial cell differentiation	1	3370.4×	8e-04	PAX8
cellular response to gonadotropin stimulus	1	2808.7×	8e-04	PAX8
otic vesicle development	1	2808.7×	8e-04	PAX8
positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	1	2808.7×	8e-04	PAX8
pronephros development	1	2407.4×	9e-04	PAX8
mesenchymal to epithelial transition involved in metanephros morphogenesis	1	2106.5×	9e-04	PAX8
mesonephros development	1	1532.0×	0.001	PAX8
urogenital system development	1	991.3×	0.002	PAX8
positive regulation of branching involved in ureteric bud morphogenesis	1	802.5×	0.002	PAX8
sensory organ development	1	674.1×	0.002	PAX8
negative regulation of cardiac muscle cell apoptotic process	1	543.6×	0.003	PAX8
thyroid gland development	1	543.6×	0.003	PAX8
ventricular septum development	1	495.6×	0.003	PAX8
branching involved in ureteric bud morphogenesis	1	366.4×	0.004	PAX8
inner ear morphogenesis	1	300.9×	0.004	PAX8
DNA-templated transcription	1	224.7×	0.006	PAX8
kidney development	1	140.4×	0.009	PAX8

Therapeutics

Drugs indicated for this disease

0 approved, 10 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bupivacaine	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Fosaprepitant	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Olanzapine	Phase 3 (in late-stage trials)
Ondansetron	Phase 3 (in late-stage trials)
Oxycodone	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Prochlorperazine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abemaciclib, Durvalumab, Fulvestrant, Tremelimumab.

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
PAX8	SORAFENIB TOSYLATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PAX8	14	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SORAFENIB TOSYLATE	4	PAX8
MITOXANTRONE HYDROCHLORIDE	4	PAX8
TEGASEROD MALEATE	4	PAX8
DAUNORUBICIN HYDROCHLORIDE	4	PAX8
DIGOXIN	4	PAX8
DOXORUBICIN HYDROCHLORIDE	4	PAX8
HEXACHLOROPHENE	4	PAX8
THIOGUANINE	4	PAX8
CHLORHEXIDINE	4	PAX8
VORINOSTAT	4	PAX8
ENPIROLINE	2	PAX8
PINAFIDE	2	PAX8
LANATOSIDE C	2	PAX8
IODOQUINOL	2	PAX8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PAX8	3	Functional:3

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).

Drug repurposing candidates

14 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)
SORAFENIB TOSYLATE	4	PAX8
MITOXANTRONE HYDROCHLORIDE	4	PAX8
TEGASEROD MALEATE	4	PAX8
DAUNORUBICIN HYDROCHLORIDE	4	PAX8
DIGOXIN	4	PAX8
DOXORUBICIN HYDROCHLORIDE	4	PAX8
HEXACHLOROPHENE	4	PAX8
THIOGUANINE	4	PAX8
CHLORHEXIDINE	4	PAX8
VORINOSTAT	4	PAX8
ENPIROLINE	2	PAX8
PINAFIDE	2	PAX8
LANATOSIDE C	2	PAX8
IODOQUINOL	2	PAX8

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PAX8
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 396.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	305
PHASE2	31
PHASE1	28
PHASE3	16
PHASE4	7
PHASE1/PHASE2	4
EARLY_PHASE1	4
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05726136	PHASE4	RECRUITING	Fluid Challenge and Plasma Volume, During Surgery
NCT06525740	PHASE4	RECRUITING	Methadone Versus Intrathecal Hydromorphone for Postoperative Pain Relief in Gynecologic Cancer Undergoing Surgery
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT03793205	PHASE4	UNKNOWN	G-CSF for the Prevention of Febrile Neutropenia in Gynecologic Cancer Patients
NCT03801031	PHASE4	TERMINATED	Sexual Dysfunction in Gynecologic Oncology Patients
NCT04258631	PHASE4	COMPLETED	Liposomal Bupivacaine With or Without Hydromorphone for the Improvement of Pain Control After Laparotomy in Patients With Gynecological Malignancies
NCT05068180	PHASE4	UNKNOWN	Low-dose Neuroleptanalgesia for Postoperative Delirium in Elderly Patients
NCT05407987	PHASE3	RECRUITING	Ferric Derisomaltose and Outcomes in the Recovery of Gynecologic Oncology: ERAS (Enhanced Recovery After Surgery)
NCT05625360	PHASE3	RECRUITING	REmotely-delivered Supportive Programs for Improving Surgical Pain and disTrEss
NCT07166042	PHASE3	RECRUITING	Guided Meditation During Radiation Therapy for Breast and Gynecological Malignancies
NCT01356329	PHASE3	SUSPENDED	Efficacy and Safety of the LovenoxTM (Enoxaparin) Versus HeparinTM Gynecologic Oncology Patients
NCT01376349	PHASE3	COMPLETED	Prasterone (Dehydroepiandrosterone) in Treating Postmenopausal Cancer Survivors With Vaginal Symptoms
NCT01435200	PHASE3	COMPLETED	Intravenous Iron in Gynecologic Cancer Patients Receiving Chemotherapy
NCT01849224	PHASE3	UNKNOWN	Randomized Trial of Exercise on Lower Extremity Edema After Lymphadenectomy in Gynecologic Cancer
NCT01871688	PHASE2/PHASE3	UNKNOWN	Pelvic Floor Rehabilitation for Gynecological Cancer Patients
NCT01974193	PHASE3	UNKNOWN	Prevention of Pelvic Lymphocele by Floseal During Pelvic Lymphadenectomy for Gynecologic Cancer
NCT02423876	PHASE3	COMPLETED	Epidural Anesthesia Within an Enhanced Recovery Pathway in Reducing Pain in Patients Undergoing Gynecologic Surgery
NCT02740114	PHASE3	TERMINATED	Wound Infiltration With Liposomal Bupivacaine vs. Standard Wound Infiltration With Bupivacaine in Patient’s Undergoing Open Gynecologic Surgery on an Enhanced Recovery Pathway
NCT03304444	PHASE3	UNKNOWN	A Comparison of Exparel to Bupivacaine in TAP Block for Abdominal Gynecologic Surgery
NCT04503668	PHASE3	TERMINATED	Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting in Gynecologic Oncology Patients
NCT04534075	PHASE3	COMPLETED	Dietary Fiber During Radiotherapy - a Placebo-controlled Randomized Trial
NCT04596800	PHASE3	UNKNOWN	Prehabilitation Plus ERAS Versus ERAS in Gynecologic Oncology: a Randomized Clinical Trial
NCT05467319	PHASE3	UNKNOWN	Ferric Derisomaltose/Iron Isomaltoside and Outcomes in the Recovery of Gynecologic Oncology ERAS
NCT05763667	PHASE3	COMPLETED	Pilot: Intraoperative TAP Block and Post-operative Pain Control for Minimally Invasive Hysterectomy for Endometrial Cancer
NCT04007770	PHASE2	ACTIVE_NOT_RECRUITING	Acupuncture Pilot Study for Cancer-related Cognitive Function
NCT04273061	PHASE2	RECRUITING	Investigating the Effects of Atezolizumab in People Whose Tumour DNA or RNA Indicates Possible Sensitivity
NCT04395079	PHASE2	ACTIVE_NOT_RECRUITING	Brachytherapy With Durvalumab or Tremelimumab for the Treatment of Patients With Platinum-Resistant, Refractory, Recurrent, or Metastatic Gynecological Malignancies
NCT04516135	PHASE2	ACTIVE_NOT_RECRUITING	Single Fraction or Multi-fraction Palliative Radiation Therapy for the Improvement of Quality of Life in Patients With Metastatic Gynecologic Cancers
NCT05296512	PHASE2	ACTIVE_NOT_RECRUITING	Pembrolizumab and Lenvatinib in Clear Cell Ovarian Cancer
NCT05559879	PHASE1/PHASE2	RECRUITING	Cabozantinib and Dostarlimab in Recurrent Gynecologic Carcinosarcoma
NCT05564377	PHASE2	RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
NCT05805358	PHASE2	NOT_YET_RECRUITING	Hyperpolarized 13C MRI for Cancer Immunotherapy
NCT06126276	PHASE2	RECRUITING	Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)
NCT06580002	PHASE2	RECRUITING	Repurposing Riluzole for Cancer-Related Cognitive Impairment: A Pilot Trial
NCT06677190	PHASE2	RECRUITING	Belzutifan in Recurrent Clear Cell Carcinoma of Gynecologic Origin
NCT06855524	PHASE2	RECRUITING	Fucoidan for Preventing Chemotherapy-Related Fatigue in Patients With Gastrointestinal or Gynecological Cancer
NCT07024784	PHASE2	RECRUITING	A Study to Assess Change in Disease Activity and Adverse Events in Adult Participants With Gynecologic Cancers Receiving Intravenous Infusion of IMGN151 as Monotherapy or in Combination With Other Therapies
NCT07039526	PHASE2	RECRUITING	Single Dose Investigator Initiated Pilot Study to Investigate CYTALUX (Pafolacianine) for Intraoperative Detection of Malignant Tissue in Subjects Undergoing Surgical Resection for Cancer.
NCT07151391	PHASE2	RECRUITING	The Use of Guarana to Treat Fatigue in Patients With Neuroendocrine Tumors and Gynecologic Cancers (Guarana Fatigue)
NCT07173101	PHASE2	RECRUITING	Clinical Investigation of the Effects of Semiconductor Embedded Therapeutic Garments on Cancer-related Cognitive Impairment in Breast and Gynecological Cancer Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PROCHLORPERAZINE	4	4
HYDROMORPHONE	4	2
INDOCYANINE GREEN ACID FORM	4	2
NERATINIB MALEATE	4	2
PRASTERONE	4	2
RILUZOLE	4	2
SELUMETINIB	4	2
ALBUMIN HUMAN	4	1
ALPELISIB	4	1
BELZUTIFAN	4	1
BINIMETINIB	4	1
BRODALUMAB	4	1
CABOZANTINIB S-MALATE	4	1
DOSTARLIMAB	4	1
FERRIC CARBOXYMALTOSE	4	1
FERRIC DERISOMALTOSE	4	1
FLUOROURACIL	4	1
GADOBUTROL	4	1
IXABEPILONE	4	1
LIDOCAINE	4	1
METHADONE	4	1
NILOTINIB HYDROCHLORIDE MONOHYDRATE	4	1
ROMIPLOSTIM	4	1
SOTORASIB	4	1
CATEQUENTINIB	3	1
IPATASERTIB	3	1
IVONESCIMAB	3	1
MONALIZUMAB	3	1
PEPPERMINT	3	1
PERFLUBUTANE	3	1