Laryngeal carcinoma

Summary

Laryngeal carcinoma (MONDO:0002358) is a cancer (an umbrella term covering 8 Mondo subtypes) with 1 cohort gene (2 GWAS associations across 6 studies; 1 CIViC-evidence somatic driver) and 108 clinical trials. Top therapeutic interventions include cisplatin, cetuximab, and docetaxel anhydrous.

At a glance

• Classification: Cancer
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 2
• Clinical trials: 108

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	laryngeal carcinoma
Mondo ID	MONDO:0002358
DOID	DOID:2600
NCIT	C4855
SNOMED CT	276975007
UMLS	C0595989
MedGen	108889
GARD	0006862
Anatomy (UBERON)	UBERON:0001737
Is cancer (heuristic)	yes

Also known as: cancer of larynx · cancer of the larynx · carcinoma of larynx · carcinoma of the larynx · laryngeal cancer · laryngeal carcinoma · laryngeal throat cancer · larynx carcinoma

Data availability: 2 GWAS associations (6 studies).

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › respiratory system cancer › larynx cancer › laryngeal carcinoma

Related subtypes (6): subglottis cancer, laryngeal cartilage cancer, supraglottis cancer, glottis cancer, laryngeal sarcoma, aryepiglottic fold cancer

Subtypes (8): glottis carcinoma, laryngeal mucoepidermoid carcinoma, carcinoma of supraglottis, subglottis carcinoma, larynx carcinoma in situ, laryngeal squamous cell carcinoma, laryngeal adenoid cystic carcinoma, laryngeal small cell carcinoma

Genetics & variants

GWAS landscape

2 GWAS associations across 6 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
rs148595717	2e-11	PRKG1	G	1.41
rs148979832	3e-11	SH3BP4 - CEP19P1	T	1.86

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90477173	Verma A	2024	2,291	448,301	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477172	Verma A	2024	546	121,214	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479778	Verma A	2024	546	121,214	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90018898	Sakaue S	2021	329	355,235	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90018678	Sakaue S	2021	300	178,426	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90435574	Zhou W	2018	258	406,821	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	1
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs148595717	10	51703813	G>C	0.003	intron_variant	PRKG1	2e-11	Tier 4: intronic/intergenic
rs148979832	2	235110837	T>G	0.001	intergenic_variant	SH3BP4 - CEP19P1	3e-11	Tier 4: intronic/intergenic

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
PTPN11	Act	ALL,AML,CLLSLL,COADREAD,GBM,LGGNOS,NBL,PAST,PCM	CIViC #4685

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTPN11	Orphanet:2499	Metachondromatosis
PTPN11	Orphanet:500	Noonan syndrome with multiple lentigines
PTPN11	Orphanet:648	Noonan syndrome
PTPN11	Orphanet:86834	Juvenile myelomonocytic leukemia

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
PTPN11	HGNC:9644	ENSG00000179295	Q06124	Tyrosine-protein phosphatase non-receptor type 11	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTPN11	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, SH2

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
dorsal motor nucleus of vagus nerve	1
globus pallidus	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTPN11	295	ubiquitous	marker	medial globus pallidus, dorsal motor nucleus of vagus nerve, globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPN11	6,009

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPN11	Q06124	115

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 52. 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
MET activates PTPN11	1	2284.0×	0.003	PTPN11
Co-inhibition by BTLA	1	2284.0×	0.003	PTPN11
STAT5 Activation	1	1631.4×	0.003	PTPN11
Netrin mediated repulsion signals	1	1268.9×	0.003	PTPN11
MAPK1 (ERK2) activation	1	1142.0×	0.003	PTPN11
STAT5 activation downstream of FLT3 ITD mutants	1	1142.0×	0.003	PTPN11
MAPK3 (ERK1) activation	1	1038.2×	0.003	PTPN11
Signaling by Leptin	1	1038.2×	0.003	PTPN11
Interleukin-6 signaling	1	951.7×	0.003	PTPN11
Activated NTRK2 signals through FRS2 and FRS3	1	951.7×	0.003	PTPN11
PECAM1 interactions	1	878.5×	0.003	PTPN11
Regulation of IFNG signaling	1	815.7×	0.003	PTPN11
Prolactin receptor signaling	1	761.3×	0.003	PTPN11
Signaling by FLT3 ITD and TKD mutants	1	761.3×	0.003	PTPN11
Spry regulation of FGF signaling	1	713.8×	0.003	PTPN11
Signal regulatory protein family interactions	1	671.8×	0.003	PTPN11
Platelet sensitization by LDL	1	671.8×	0.003	PTPN11
Regulation of RUNX1 Expression and Activity	1	671.8×	0.003	PTPN11
GAB1 signalosome	1	634.4×	0.003	PTPN11
PI-3K cascade:FGFR3	1	634.4×	0.003	PTPN11
Tie2 Signaling	1	601.0×	0.003	PTPN11
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1	601.0×	0.003	PTPN11
PI-3K cascade:FGFR4	1	571.0×	0.003	PTPN11
Signaling by CSF3 (G-CSF)	1	571.0×	0.003	PTPN11
FRS-mediated FGFR3 signaling	1	543.8×	0.003	PTPN11
Co-inhibition by CTLA4	1	519.1×	0.003	PTPN11
Co-inhibition by PD-1	1	519.1×	0.003	PTPN11
PI-3K cascade:FGFR1	1	519.1×	0.003	PTPN11
Interleukin-37 signaling	1	519.1×	0.003	PTPN11
PI-3K cascade:FGFR2	1	496.5×	0.003	PTPN11

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
negative regulation of cortisol secretion	1	16852.0×	0.002	PTPN11
negative regulation of growth hormone secretion	1	16852.0×	0.002	PTPN11
microvillus organization	1	8426.0×	0.002	PTPN11
intestinal epithelial cell migration	1	8426.0×	0.002	PTPN11
cerebellar cortex formation	1	5617.3×	0.002	PTPN11
regulation of type I interferon-mediated signaling pathway	1	4213.0×	0.002	PTPN11
ERBB signaling pathway	1	3370.4×	0.002	PTPN11
negative regulation of neutrophil activation	1	2407.4×	0.003	PTPN11
positive regulation of hormone secretion	1	1685.2×	0.003	PTPN11
genitalia development	1	1685.2×	0.003	PTPN11
positive regulation of lipopolysaccharide-mediated signaling pathway	1	1532.0×	0.003	PTPN11
atrioventricular canal development	1	1532.0×	0.003	PTPN11
regulation of protein export from nucleus	1	1532.0×	0.003	PTPN11
Bergmann glial cell differentiation	1	1532.0×	0.003	PTPN11
negative regulation of cell adhesion mediated by integrin	1	1296.3×	0.003	PTPN11
neurotrophin TRK receptor signaling pathway	1	1053.2×	0.003	PTPN11
positive regulation of ossification	1	936.2×	0.003	PTPN11
peptidyl-tyrosine dephosphorylation	1	887.0×	0.003	PTPN11
hormone metabolic process	1	887.0×	0.003	PTPN11
positive regulation of insulin receptor signaling pathway	1	842.6×	0.003	PTPN11
organ growth	1	732.7×	0.003	PTPN11
regulation of protein-containing complex assembly	1	732.7×	0.003	PTPN11
platelet formation	1	702.2×	0.003	PTPN11
megakaryocyte development	1	702.2×	0.003	PTPN11
negative regulation of chondrocyte differentiation	1	674.1×	0.003	PTPN11
positive regulation of intracellular signal transduction	1	648.1×	0.003	PTPN11
platelet-derived growth factor receptor signaling pathway	1	561.7×	0.004	PTPN11
negative regulation of T cell activation	1	526.6×	0.004	PTPN11
negative regulation of type I interferon production	1	495.6×	0.004	PTPN11
negative regulation of insulin secretion	1	495.6×	0.004	PTPN11

Therapeutics

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
PTPN11	ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTPN11	8	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ESTRAMUSTINE PHOSPHATE	4	PTPN11
ENOXOLONE	2	PTPN11
CEFSULODIN	2	PTPN11
BATOPROTAFIB	2	PTPN11
VOCIPROTAFIB	2	PTPN11
JAB-3068	1	PTPN11
PF-07284892	1	PTPN11
BBP-398	1	PTPN11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PTPN11	588	Binding:585, Functional:2, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPN11	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PTPN11	588

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

8 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)
ESTRAMUSTINE PHOSPHATE	4	PTPN11
ENOXOLONE	2	PTPN11
CEFSULODIN	2	PTPN11
BATOPROTAFIB	2	PTPN11
VOCIPROTAFIB	2	PTPN11
JAB-3068	1	PTPN11
PF-07284892	1	PTPN11
BBP-398	1	PTPN11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PTPN11
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: 108.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	51
PHASE2	30
PHASE1	12
PHASE3	8
PHASE1/PHASE2	3
PHASE2/PHASE3	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05063552	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers
NCT05721755	PHASE3	ACTIVE_NOT_RECRUITING	Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT06589804	PHASE3	RECRUITING	Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
NCT06957938	PHASE3	NOT_YET_RECRUITING	Comparing Neoadjuvant Chemotherapy Combined With PD-1 Inhibitor Versus Neoadjuvant Chemotherapy in Locally Advanced Laryngeal and Hypopharyngeal Carcinoma
NCT07441681	PHASE3	NOT_YET_RECRUITING	Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
NCT00117572	PHASE3	COMPLETED	Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer (DeCIDE)
NCT00147732	PHASE3	COMPLETED	Randomized Trial of ARCON in Larynx Cancer
NCT00467948	PHASE3	COMPLETED	Comparison of 2 Cefazolin Prophylactic Protocol in Laryngectomy Patients
NCT03258554	PHASE2/PHASE3	COMPLETED	Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Locoregionally Advanced Head and Neck Cancer Who Cannot Take Cisplatin
NCT05369234	PHASE3	COMPLETED	Effects of Oral Aloe Vera Juice on Chemotherapy and Radiation-induced Oral Mucositis and Esophagitis
NCT00593840	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Trial Evaluating Elimination of Radiation Therapy
NCT02734537	PHASE2	RECRUITING	Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IVA Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery
NCT04030455	PHASE2	ACTIVE_NOT_RECRUITING	Cisplatin, Docetaxel, and Pembrolizumab in Treating Patients With Stage II-III Laryngeal Cancer
NCT04862650	PHASE2	ACTIVE_NOT_RECRUITING	Cemiplimab, Low-Dose Paclitaxel and Carboplatin for the Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT05075980	PHASE2	ACTIVE_NOT_RECRUITING	Intensity Modulated Proton or X-Ray Therapy After Surgery for Treatment of Head and Neck Cancer, the HEADLIGHT Study
NCT05136196	PHASE2	RECRUITING	BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
NCT05172258	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Addition of an Anti-cancer Drug, Ipatasertib, to the Usual Immunotherapy Treatment (Pembrolizumab) in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
NCT06137378	PHASE2	RECRUITING	European Larynx Organ Preservation Study (ELOS) [MK-3475-C44]
NCT06532279	PHASE2	RECRUITING	Testing the Addition of the Drug BMX-001, a Radioprotector, or a Placebo to the Usual Chemoradiation Therapy for Patients With Head and Neck 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
NCT06636734	PHASE2	RECRUITING	Lovastatin and Pembrolizumab for the Treatment of Patients With Recurrent or Metastatic Head and Neck Cancer, LAPP Trial
NCT06980038	PHASE2	RECRUITING	Testing Whether Cemiplimab (REGN2810) Plus CDX-1140 Given Prior to Surgery Are Better Than Cemiplimab (REGN2810) Alone in Patients With Stage III-IV Head and Neck Cancer
NCT06997068	PHASE2	RECRUITING	Methotrexate, Erlotinib, and Celecoxib for the Treatment of Recurrent/Metastatic Head and Neck Cancer in a Rural Midwest United States Population
NCT07195734	PHASE2	RECRUITING	Testing the Addition of Chemotherapy or Chemo-Immunotherapy to the Usual Surgery for Advanced Head and Neck Cancer
NCT07209189	PHASE2	RECRUITING	Neoadjuvant Chemotherapy and Programmed Cell Death Protein 1(PD-1) Inhibition for Head and Neck Cancer Treatment De-escalation (NeoScorch HN)
NCT00026975	PHASE2	COMPLETED	Efficacy of Hyperbaric Oxygen Therapy in Laryngectomy Patients
NCT00462735	PHASE2	COMPLETED	Fluorouracil, Hydroxyurea, Cetuximab and Twice-daily Intensity Radiation Therapy for Advanced Head and Neck Cancer
NCT00508664	PHASE2	COMPLETED	Docetaxel, Cisplatin (TP) + Radiation +/- Cetuximab in Larynx Carcinoma (CA)
NCT00599131	PHASE2	TERMINATED	Cetuximab and Radiation Therapy in Laryngeal Cancer Patients Who Have Responded to One Cycle of Chemotherapy (SPORE)
NCT00827164	PHASE2	COMPLETED	Resistance Training During Radiation Therapy for Pharyngeal or Laryngeal Cancer
NCT00970502	PHASE1/PHASE2	COMPLETED	Erlotinib, Celecoxib and Reirradiation for Recurrent Head and Neck Cancer
NCT01435252	PHASE2	COMPLETED	A Phase II Study In Patients With Advanced Head And Neck Cancer Of Standard Chemoradiation And Add-On Cetuximab
NCT01633541	PHASE2	COMPLETED	Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Organ Preservation In Adults With Advanced Laryngeal Cancer
NCT01806675	PHASE1/PHASE2	COMPLETED	18F-FPPRGD2 PET/CT or PET/MRI in Predicting Early Response in Patients With Cancer Receiving Anti-Angiogenesis Therapy
NCT02062632	PHASE2	TERMINATED	Doxepin Hydrochloride in Treating Esophageal Pain in Patients With Thoracic Cancer Receiving Radiation Therapy to the Thorax With or Without Chemotherapy
NCT02849314	PHASE1/PHASE2	COMPLETED	Combination of Cryosurgey and NK Immunotherapy for Recurrent Laryngeal Cancer
NCT04162873	PHASE2	TERMINATED	Celecoxib Through Surgery and Radiation Therapy for the Treatment of Advanced Head and Neck Cancer
NCT04525066	PHASE2	COMPLETED	Phonosurgical Augmentation After Laser Resection of Early Glottic Carcinoma
NCT04541355	PHASE2	COMPLETED	Sodium Thiosulfate in Preventing Ototoxicity for Squamous Cell Cancer Patients Undergoing Chemoradiation With Cisplatin

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CISPLATIN	4	18
CETUXIMAB	4	3
DOCETAXEL ANHYDROUS	4	3
HYDROXYUREA	4	2
ATEZOLIZUMAB	4	1
CABOZANTINIB	4	1
CEFAZOLIN	4	1
CEMIPLIMAB	4	1
DOXEPIN HYDROCHLORIDE	4	1
DURVALUMAB	4	1
HYALURONIC ACID	4	1
ISOSORBIDE	4	1
LOVASTATIN	4	1
SODIUM FLUORIDE F 18	4	1
SODIUM THIOSULFATE	4	1
SUCRALFATE	4	1
IPATASERTIB	3	2
BUPARLISIB	3	1
XEVINAPANT	3	1
CAMONSERTIB	2	1
ELIMUSERTIB	1	1
NEDISERTIB	1	1
CHEMBL1510899	0	1
CHEMBL5412235	0	1
CHEMBL1200462	0	1
CHEMBL3753202	0	1