Hypopharynx cancer

Summary

Hypopharynx cancer (MONDO:0005806) is a cancer with 2 cohort genes (2 GWAS associations across 1 studies) and 46 clinical trials. Top therapeutic interventions include docetaxel anhydrous, carboplatin, and sacituzumab govitecan.

At a glance

• Classification: Cancer
• Cohort genes: 2
• GWAS associations: 2
• Clinical trials: 46

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypopharynx cancer
Mondo ID	MONDO:0005806
EFO	EFO:0007321
MeSH	D007012
DOID	DOID:8533
ICD-10-CM	C13
ICD-11	826670225
NCIT	C7190
SNOMED CT	303012000
UMLS	C0153398
MedGen	102266
GARD	0009334
Anatomy (UBERON)	UBERON:0001051
Is cancer (heuristic)	yes

Also known as: hypopharyngeal cancer · hypopharynx pharynx cancer · hypural pharynx cancer · malignant hypopharyngeal neoplasm · malignant hypopharyngeal tumor · malignant hypopharyngeal tumour · malignant neoplasm of hypopharynx · malignant neoplasm of ill-defined sites within the lip and oral cavity · malignant neoplasm of other specified hypopharyngeal site · malignant neoplasm of other specified sites of hypopharynx · malignant neoplasm of posterior hypopharyngeal wall · malignant neoplasm of posterior wall of hypopharynx · malignant neoplasm of the hypopharynx · malignant tumor of hypopharynx · malignant tumor of posterior wall of hypopharynx · malignant tumor of the hypopharynx · malignant tumour of posterior wall of hypopharynx · malignant tumour of the hypopharynx · pharynx cancer of hypopharynx

Data availability: 2 GWAS associations (1 study).

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › respiratory system cancer › pharynx cancer › hypopharynx cancer

Related subtypes (4): pharyngeal squamous cell carcinoma, oropharynx cancer, pharyngeal adenoid cystic carcinoma, malignant tumor of nasopharynx

Subtypes (4): postcricoid region cancer, aryepiglottic fold cancer, pyriform sinus cancer, hypopharyngeal carcinoma

Genetics & variants

GWAS landscape

2 GWAS associations across 1 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs142021700	3e-09	RTTN	C	3.95
rs77045180	1e-07	AKR1C1	T	2.51

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010285	Shete S	2020	394	4,493	A genome-wide association study identifies two novel susceptible regions for squamous cell carcinoma of the head and neck.

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	1

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs142021700	18	70034347	T>C	0.01	intron_variant	RTTN	3e-09	Tier 4: intronic/intergenic
rs77045180	10	4981859	G>C,T	0.02	3_prime_UTR_variant	AKR1C1	1e-07	Tier 2: splice/UTR

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RTTN	Orphanet:468631	Microcephalic cortical malformations-short stature due to RTTN deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RTTN	HGNC:18654	ENSG00000176225	Q86VV8	Rotatin	gwas
AKR1C1	HGNC:384	ENSG00000187134	Q04828	Aldo-keto reductase family 1 member C1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RTTN	Rotatin	Involved in the genetic cascade that governs left-right specification.
AKR1C1	Aldo-keto reductase family 1 member C1	Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RTTN	Other/Unknown	no		ARM-like, ARM-type_fold, Rotatin_N
AKR1C1	Enzyme (other)	yes	1.1.1.149	Aldo/ket_reductase_CS, AKR, NADP_OxRdtase_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1
islet of Langerhans	1
mucosa of stomach	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RTTN	238	ubiquitous	marker	secondary oocyte, oocyte, male germ line stem cell (sensu Vertebrata) in testis
AKR1C1	162	ubiquitous	marker	islet of Langerhans, mucosa of stomach, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RTTN	1,555
AKR1C1	73

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AKR1C1	Q04828	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RTTN	Q86VV8	77.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 2 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
Prednisone ADME	1	1268.9×	0.006	AKR1C1
Synthesis of bile acids and bile salts via 24-hydroxycholesterol	1	878.5×	0.006	AKR1C1
Synthesis of bile acids and bile salts via 27-hydroxycholesterol	1	761.3×	0.006	AKR1C1
Bile acid and bile salt metabolism	1	496.5×	0.006	AKR1C1
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol	1	456.8×	0.006	AKR1C1
Synthesis of bile acids and bile salts	1	407.9×	0.006	AKR1C1
Metabolism of fat-soluble vitamins	1	380.7×	0.006	AKR1C1
Visual phototransduction	1	259.6×	0.007	AKR1C1
Retinoid metabolism and transport	1	248.3×	0.007	AKR1C1
Drug ADME	1	228.4×	0.007	AKR1C1
Metabolism of steroids	1	137.6×	0.010	AKR1C1
Metabolism of vitamins and cofactors	1	116.5×	0.011	AKR1C1
Sensory Perception	1	95.2×	0.012	AKR1C1
Metabolism of lipids	1	31.6×	0.034	AKR1C1
Metabolism	1	11.6×	0.086	AKR1C1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to jasmonic acid stimulus	1	2106.5×	0.004	AKR1C1
ciliary basal body organization	1	1685.2×	0.004	RTTN
progesterone metabolic process	1	842.6×	0.004	AKR1C1
daunorubicin metabolic process	1	766.0×	0.004	AKR1C1
intestinal cholesterol absorption	1	702.2×	0.004	AKR1C1
centriole-centriole cohesion	1	648.1×	0.004	RTTN
doxorubicin metabolic process	1	648.1×	0.004	AKR1C1
bile acid metabolic process	1	495.6×	0.005	AKR1C1
retinal metabolic process	1	468.1×	0.005	AKR1C1
prostaglandin metabolic process	1	421.3×	0.005	AKR1C1
centriole replication	1	366.4×	0.005	RTTN
bile acid and bile salt transport	1	324.1×	0.005	AKR1C1
digestion	1	312.1×	0.005	AKR1C1
positive regulation of reactive oxygen species metabolic process	1	255.3×	0.005	AKR1C1
retinoid metabolic process	1	247.8×	0.005	AKR1C1
determination of left/right symmetry	1	127.7×	0.009	RTTN
epithelial cell differentiation	1	87.8×	0.013	AKR1C1
cholesterol homeostasis	1	78.0×	0.013	AKR1C1
xenobiotic metabolic process	1	74.6×	0.013	AKR1C1

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): Toripalimab.

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
AKR1C1	DIAZEPAM

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AKR1C1	9	4
RTTN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DIAZEPAM	4	AKR1C1
GLIMEPIRIDE	4	AKR1C1
BENZBROMARONE	4	AKR1C1
MECLOFENAMIC ACID	4	AKR1C1
FLURBIPROFEN	4	AKR1C1
INDOMETHACIN	4	AKR1C1
MEFENAMIC ACID	4	AKR1C1
MEDROXYPROGESTERONE ACETATE	4	AKR1C1
FLUFENAMIC ACID	2	AKR1C1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
AKR1C1	100	Binding:91, ADMET:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AKR1C1	1.1.1.149, 1.1.1.270, 1.1.1.357, 1.1.1.50, 1.3.1.20	20alpha-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid 3-dehydrogenase, 3alpha-hydroxysteroid 3-dehydrogenase, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific), trans-1,2-dihydrobenzene-1,2-diol dehydrogenase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
AKR1C1	100

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

9 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)
DIAZEPAM	4	AKR1C1
GLIMEPIRIDE	4	AKR1C1
BENZBROMARONE	4	AKR1C1
MECLOFENAMIC ACID	4	AKR1C1
FLURBIPROFEN	4	AKR1C1
INDOMETHACIN	4	AKR1C1
MEFENAMIC ACID	4	AKR1C1
MEDROXYPROGESTERONE ACETATE	4	AKR1C1
FLUFENAMIC ACID	2	AKR1C1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	AKR1C1
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	RTTN

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)
RTTN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 46.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	17
Not specified	17
PHASE3	6
PHASE1	4
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06706401	PHASE3	RECRUITING	Lymphocyte-Sparing And Radio-Immunotherapy in Head and Neck Carcinoma
NCT00158652	PHASE3	COMPLETED	Accelerated Radiotherapy and Concomitant Chemo-radiotherapy in HNSCC
NCT00158678	PHASE3	COMPLETED	IMRT Plus Cisplatin Versus Conventional Radiotherapy Plus Cisplatin in Stage III-IV HNSCC
NCT00162708	PHASE2/PHASE3	COMPLETED	Very Intense Radiotherapy-Chemotherapy Regimen in Advanced HNSCC
NCT00169182	PHASE3	COMPLETED	Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma
NCT01066741	PHASE3	TERMINATED	Prevention of Radiation-induced Severe Oral Mucositis in Oral Cavity, Oropharynx, Hypopharynx, and Cavum Cancer
NCT04502641	PHASE3	UNKNOWN	Induction Chemotherapy in Locally Advanced Hypopharyngeal Carcinoma: a Randomised Phase 3 Trial
NCT06039631	PHASE2	RECRUITING	Neoadjuvant Chemoimmunotherapy Followed By Radiation Or Organ Preservation Surgery In Laryngeal/Hypopharyngeal Cancer
NCT06554028	PHASE2	NOT_YET_RECRUITING	Tislelizumab and Induction Chemotherapy for Larynx Preservation in Resectable Advanced Laryngeal/Hypopharyngeal Cancer
NCT06611137	PHASE2	RECRUITING	SBRT Followed by Chemoimmunotherapy of Toripalimab Plus Docetaxel and Cisplatin for Larynx Preservation in Patients with Locally Regionally Advanced Squamous Cell Carcinoma of the Larynx and Hypopharynx
NCT06997068	PHASE2	RECRUITING	Methotrexate, Erlotinib, and Celecoxib for the Treatment of Recurrent/Metastatic Head and Neck Cancer in a Rural Midwest United States Population
NCT07063212	PHASE2	RECRUITING	A Study of Sacituzumab Govitecan in Combination With Cetuximab in People With Head and Neck Squamous Cell Cancer (HNSCC)
NCT07137039	PHASE2	NOT_YET_RECRUITING	Neoadjuvant Treatment of Locally Advanced Hypopharyngeal Cancer With Adebrelimab Combined With TP Chemotherapy Regimen
NCT00169247	PHASE2	COMPLETED	Radiotherapy With Cisplatin Versus Radiotherapy With Cetuximab After Induction Chemotherapy for Larynx Preservation
NCT01312350	PHASE2	COMPLETED	Neoadjuvant Chemotherapy for Locally Advanced Squamous Cell Cancer of the Head and Neck (SCCHN)
NCT01435252	PHASE2	COMPLETED	A Phase II Study In Patients With Advanced Head And Neck Cancer Of Standard Chemoradiation And Add-On Cetuximab
NCT01516996	PHASE2	UNKNOWN	Safety and Efficacy Study of Nimotuzumab Plus Neoadjuvant and Concurrent Chemoradiotherapy to Treat Oropharynx and Hypopharynx Cancer
NCT01806675	PHASE1/PHASE2	COMPLETED	18F-FPPRGD2 PET/CT or PET/MRI in Predicting Early Response in Patients With Cancer Receiving Anti-Angiogenesis Therapy
NCT03082534	PHASE2	COMPLETED	Pembrolizumab Combined With Cetuximab for Treatment of Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma
NCT03096808	PHASE2	COMPLETED	Adaptive Radiotherapy for Head and Neck Cancer
NCT03558035	PHASE2	UNKNOWN	New Strategy of Improving Treatment Outcome and Larynx-preservation Rate in Locally Advanced Hypopharyngeal Carcinoma
NCT04539600	PHASE2	UNKNOWN	Induction Chemotherapy Combined With Camrelizumab in Locoregionally Advanced Hypopharyngeal Cancer
NCT04995120	PHASE2	UNKNOWN	Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma
NCT05420597	PHASE2	UNKNOWN	Induction Chemotherapy and Toripalimab Followed by Radiotherapy in Unresectable Laryngeal/Hypopharyngeal Carcinoma
NCT05860335	PHASE2	UNKNOWN	Efficacy and Safety of Toripalimab Combined With AP-induced Chemotherapy Followed in Non-metastatic IVB Hypopharyngeal Cancer
NCT00080028	PHASE1	TERMINATED	Motexafin Gadolinium With Chemotherapy and Radiation Therapy for the Treatment of Advanced Head and Neck Cancer
NCT02113878	PHASE1	COMPLETED	Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck
NCT02586207	PHASE1	COMPLETED	Pembrolizumab in Combination With CRT for LA-SCCHN
NCT04892875	PHASE1	WITHDRAWN	A Study of Concurrent Chemoradiation in Combination With or Without PD1 Inhibitor AB122 Adenosine 2a Receptor / Adenosine 2b Receptor Inhibitor AB928 Therapies in Locally Advanced Head and Neck Cancers
NCT02012699	Not specified	RECRUITING	Integrated Cancer Repository for Cancer Research
NCT05337631	Not specified	RECRUITING	Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy
NCT05375266	Not specified	RECRUITING	Immune Biomarker Study for Head and Neck Cancer
NCT05798780	Not specified	ACTIVE_NOT_RECRUITING	The ENHANCE Study: Exercise and Nutrition in Head And Neck CancEr Survivors
NCT05894070	Not specified	RECRUITING	The Voice as a Tool to Detect Recurrence of Laryngeal and Hypopharyngeal Cancer
NCT07532538	Not specified	NOT_YET_RECRUITING	A Machine Learning-Based Risk Prediction Model for Head and Neck Cancerous Lesions
NCT00173381	Not specified	UNKNOWN	The Role of Lymphangiogenesis in Head and Neck Cancer Metastasis
NCT00174096	Not specified	UNKNOWN	The Role of Stromal Cell-Derived Factor-1 (SDF-1)/CXC Chemokine Receptor 4 (CXCR4) in Metastasis of Laryngeal and Hypopharyngeal Squamous Cell Carcinoma
NCT00302562	Not specified	UNKNOWN	The Role of MMPs in the CXCL12-Induced Invasion of Laryngeal and Hypopharyngeal Squamous Cell Carcinoma
NCT00473564	Not specified	COMPLETED	Robotic Assisted Surgery in Upper Aerodigestive Tract Surgery
NCT01053546	Not specified	TERMINATED	Effects of Swallowing Exercises on Patients Undergoing Radiation Treatment for Head and Neck Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DOCETAXEL ANHYDROUS	4	3
CARBOPLATIN	4	1
SACITUZUMAB GOVITECAN	4	1
TRETINOIN	4	1
5-FLUORONICOTINIC ACID	3	1
BUPARLISIB	3	1
NIMOTUZUMAB	3	1
PLATINUM	3	1
ZIMBERELIMAB	3	1
ETRUMADENANT	2	1
CHEMBL1510899	0	1