Oral cavity cancer

Summary

Oral cavity cancer (MONDO:0005515) is a cancer (an umbrella term covering 11 Mondo subtypes) with 12 cohort genes (40 GWAS associations across 9 studies) and 40 clinical trials. Top therapeutic interventions include celecoxib, dacomitinib anhydrous, and naproxen sodium.

At a glance

• Classification: Cancer
• Umbrella term: 11 Mondo subtypes
• Cohort genes: 12
• GWAS associations: 40
• Clinical trials: 40

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oral cavity cancer
Mondo ID	MONDO:0005515
EFO	EFO:0005570
DOID	DOID:8618
NCIT	C9314
SNOMED CT	363505006
UMLS	C0153381
MedGen	56298
Anatomy (UBERON)	UBERON:0000167
Is cancer (heuristic)	yes

Also known as: cancer of oral cavity · malignant mouth neoplasm · malignant mouth tumor · malignant mouth tumour · malignant neoplasm of anterior portion of floor of mouth · malignant neoplasm of floor of mouth · malignant neoplasm of lateral floor of mouth · malignant neoplasm of lateral portion of floor of mouth · malignant neoplasm of mouth · malignant neoplasm of oral cavity · malignant neoplasm of the mouth · malignant oral cavity neoplasm · malignant oral cavity tumor · malignant oral cavity tumour · malignant tumor of anterior floor of mouth · malignant tumor of lateral floor of mouth · malignant tumor of mouth · malignant tumor of oral cavity · malignant tumor of the floor of the mouth · malignant tumor of the mouth (+7 more)

Data availability: 40 GWAS associations (9 studies).

Disease family

An umbrella term covering 11 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › digestive system cancer › oral cavity cancer

Related subtypes (14): gastric cancer, jaw cancer, liver cancer, gastrointestinal lymphoma, gallbladder cancer, pharynx cancer, intestinal cancer, spleen cancer, digestive system carcinoma, esophageal cancer, malignant pancreatic neoplasm, malignant tumor of floor of mouth, digestive system melanoma, gastroesophageal cancer

Subtypes (11): soft palate cancer, tongue cancer, cheek mucosa cancer, salivary gland cancer, retromolar area cancer, hard palate cancer, vestibule of mouth cancer, gingival cancer, lip cancer, oral cavity carcinoma, oral rhabdomyosarcoma

Genetics & variants

GWAS landscape

40 GWAS associations across 9 studies. Top hits map to 27 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1058026	2e-11	HLA-B	?
rs10462706	8e-11	CLPTM1L	C	1.37
rs1229984	1e-09	ADH1B	G	1.74
rs1049055	3e-09	HLA-DQB1	T	1.28
rs3828805	3e-09	HLA-DQB1	C	1.3
rs8181047	4e-09	CDKN2B-AS1	A	1.24
rs10851478	1e-08	FAM227B	A	1.22
rs928674	2e-08	LAMC3	G	1.33
rs6547741	4e-08	GPN1	G	1.2
rs201982221	5e-08	LHPP	?	1.74
rs692309	5e-08	DTWD1 - ATP8B4	C	0.82
rs3129780	6e-08	HLA-DQB1 - MTCO3P1	A	1.24
rs1800628	7e-08	TNF - LTB	A	1.4
rs35189640	8e-08	ABTB3	T	1.79
rs3823363	1e-07	POLR1HASP, POLR1HASP, HCG9	A	0.82
rs2398180	3e-07	NR2F2-AS1	T	1.2
rs77452476	3e-07	LAMC3	G	1.29
rs150481896	4e-07	SNAP29	A	2.17
rs11705249	6e-07	LINC01310 - NHIP	T	1.52
rs1479575211	7e-07	DIRC3	?	0.77
rs10206237	8e-07	DYSF - RPS20P10	G	0.74
rs73224896	1e-06	LINC02472 - U6	T	1.56
rs2097442	1e-06	HLA-DRA - HLA-DRB9	A	1.24
rs506770	2e-06	HSPA1A	C	1.24
rs10961555	2e-06	NFIB-AS1 - ZDHHC21	C	0.82
rs35292478	2e-06	LDHA - LDHC	C	1.24
rs8049988	3e-06	FTO	G	1.22
rs7110476	3e-06	TRIM5	G	0.82
rs1051512	4e-06	TFAP2A, TFAP2A-AS1	T	1.72
rs2523608	4e-06	HLA-B	A	0.84

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST003858	Lesseur C	2016	2,717	5,984	Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
GCST90085701	Ferreiro-Iglesias A	2021	2,359	0	Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.
GCST90651240	Liu TY	2025	2,032	231,112	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST012237	Lesseur C	2016	1,223	2,928	Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
GCST012238	Lesseur C	2016	1,135	2,329	Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
GCST010287	Shete S	2020	631	4,493	A genome-wide association study identifies two novel susceptible regions for squamous cell carcinoma of the head and neck.
GCST012239	Lesseur C	2016	340	0	Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
GCST90041793	Jiang L	2021	156	456,192	A generalized linear mixed model association tool for biobank-scale data.
GCST90041888	Jiang L	2021	101	456,175	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	1
Tier 2: splice/UTR	2
Tier 3: regulatory	2
Tier 4: intronic/intergenic	29

MAF distribution

Bucket	Variants
common (>=0.05)	32
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	21
intergenic_variant	6
regulatory_region_variant	2
3_prime_UTR_variant	1
missense_variant	1
5_prime_UTR_variant	1
synonymous_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1058026	6	31353908	A>C	0.05	3_prime_UTR_variant	HLA-B	2e-11	Tier 2: splice/UTR
rs10462706	5	1343679	C>G,T	0.16	intron_variant	CLPTM1L	8e-11	Tier 4: intronic/intergenic
rs1229984	4	99318162	T>A,C,G	0.06	missense_variant	ADH1B	1e-09	Tier 1: coding
rs1049055	6	32666610	C>A,G,T	0.22	5_prime_UTR_variant	HLA-DQB1	3e-09	Tier 2: splice/UTR
rs3828805	6	32668343	T>A,C,G	0.05	regulatory_region_variant	HLA-DQB1	3e-09	Tier 3: regulatory
rs8181047	9	22064466	A>C,G,T	0.24	intron_variant	CDKN2B-AS1	4e-09	Tier 4: intronic/intergenic
rs10851478	15	49536822	T>C	0.05	intron_variant	FAM227B	1e-08	Tier 4: intronic/intergenic
rs928674	9	131076637	A>G,T	0.12	intron_variant	LAMC3	2e-08	Tier 4: intronic/intergenic
rs6547741	2	27633057	G>A,C,T	0.46	intron_variant	GPN1	4e-08	Tier 4: intronic/intergenic
rs201982221	10	124468877	CCAG>C		intron_variant	LHPP	5e-08	Tier 4: intronic/intergenic
rs692309	15	49706485	T>A,C	0.05	intergenic_variant	DTWD1 - ATP8B4	5e-08	Tier 4: intronic/intergenic
rs3129780	6	32679924	T>A,C	0.36	intergenic_variant	HLA-DQB1 - MTCO3P1	6e-08	Tier 4: intronic/intergenic
rs1800628	6	31579073	G>A,C	0.07	intergenic_variant	TNF - LTB	7e-08	Tier 4: intronic/intergenic
rs35189640	12	107582831	C>T	0.05	intron_variant	ABTB3	8e-08	Tier 4: intronic/intergenic
rs3823363	6	29975938	C>T	0.05	intron_variant	POLR1HASP, POLR1HASP, HCG9	1e-07	Tier 4: intronic/intergenic
rs2398180	15	96319940	C>A,G,T	0.47	intron_variant	NR2F2-AS1	3e-07	Tier 4: intronic/intergenic
rs77452476	9	131087186	T>G	0.05	intron_variant	LAMC3	3e-07	Tier 4: intronic/intergenic
rs150481896	22	20877573	G>A	0.05	intron_variant	SNAP29	4e-07	Tier 4: intronic/intergenic
rs11705249	22	48962509	G>A,T	0.05	intron_variant	LINC01310 - NHIP	6e-07	Tier 4: intronic/intergenic
rs1479575211	2	217406087	C>G		intron_variant	DIRC3	7e-07	Tier 4: intronic/intergenic
rs10206237	2	71858661	A>C,G,T	0.05	intergenic_variant	DYSF - RPS20P10	8e-07	Tier 4: intronic/intergenic
rs73224896	4	29367523	A>T	0.05	intergenic_variant	LINC02472 - U6	1e-06	Tier 4: intronic/intergenic
rs2097442	6	32454414	G>A,T	0.05	intron_variant	HLA-DRA - HLA-DRB9	1e-06	Tier 4: intronic/intergenic
rs506770	6	31817451	G>A,C,T	0.05	synonymous_variant	HSPA1A	2e-06	Tier 4: intronic/intergenic
rs10961555	9	14533586	G>C	0.05	non_coding_transcript_exon_variant	NFIB-AS1 - ZDHHC21	2e-06	Tier 4: intronic/intergenic
rs35292478	11	18408444	A>C	0.05	regulatory_region_variant	LDHA - LDHC	2e-06	Tier 3: regulatory
rs8049988	16	54008129	A>C,G,T	0.05	intron_variant	FTO	3e-06	Tier 4: intronic/intergenic
rs7110476	11	5775532	A>G	0.05	intergenic_variant	TRIM5	3e-06	Tier 4: intronic/intergenic
rs1051512	6	10415901	C>A,G,T	0.05	intron_variant	TFAP2A, TFAP2A-AS1	4e-06	Tier 4: intronic/intergenic
rs2523608	6	31354782	G>A,C,T	0.05	intron_variant	HLA-B	4e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HLA-DQB1	Orphanet:2073	Narcolepsy type 1
HLA-DQB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DQB1	Orphanet:703	Bullous pemphigoid
HLA-DQB1	Orphanet:83465	Narcolepsy type 2
HLA-DQB1	Orphanet:930	Idiopathic achalasia
LAMC3	Orphanet:280640	Occipital pachygyria and polymicrogyria

Cohort genes → proteins

12 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GPN1	HGNC:17030	ENSG00000198522	Q9HCN4	GPN-loop GTPase 1	gwas
CLPTM1L	HGNC:24308	ENSG00000049656	Q96KA5	Lipid scramblase CLPTM1L	gwas
ADH1B	HGNC:250	ENSG00000196616	P00325	All-trans-retinol dehydrogenase [NAD(+)] ADH1B	gwas
SPATA31H1	HGNC:25275	ENSG00000221843	Q68DN1	Spermatogenesis-associated protein 31H1	gwas
CCDC121	HGNC:25833	ENSG00000176714	Q6ZUS5	Coiled-coil domain-containing protein 121	gwas
ZNF512	HGNC:29380	ENSG00000243943	Q96ME7	Zinc finger protein 512	gwas
CDKN2B-AS1	HGNC:34341	ENSG00000240498		CDKN2B and CDKN2A antisense cis and trans regulatory RNA 1	gwas
AIF1	HGNC:352	ENSG00000204472	P55008	Allograft inflammatory factor 1	gwas
NR2F2-AS1	HGNC:44222	ENSG00000247809		NR2F2 antisense RNA 1	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
LAMC3	HGNC:6494	ENSG00000050555	Q9Y6N6	Laminin subunit gamma-3	gwas
MICB	HGNC:7091	ENSG00000204516	Q29980	MHC class I polypeptide-related sequence B	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GPN1	GPN-loop GTPase 1	Small GTPase involved in the correct assembly of RNA polymerase II (RNAPII) complex, ensuring proper nuclear import of RNAPII.
CLPTM1L	Lipid scramblase CLPTM1L	Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to th…
ADH1B	All-trans-retinol dehydrogenase [NAD(+)] ADH1B	Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism.
ZNF512	Zinc finger protein 512	Sequence-specific DNA-binding protein that recognizes repetitive and non-consecutive TTC sequences in pericentric repeat and initiates heterochromatin formation through interaction with SUV39H1/2 methyltransferases which catalyze histone H…
AIF1	Allograft inflammatory factor 1	Actin-binding protein that enhances membrane ruffling and RAC activation.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
LAMC3	Laminin subunit gamma-3	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
MICB	MHC class I polypeptide-related sequence B	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8+ alphabeta T-cells.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 9 · Druggable fraction: 0.17

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
Antibody/Immunoglobulin	2	4.9×	0.185
Other/Unknown	9	1.3×	0.221
Transcription factor	1	0.7×	0.788

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GPN1	Other/Unknown	no		AAA+_ATPase, Gpn, P-loop_NTPase
CLPTM1L	Other/Unknown	no		CLPTM1
ADH1B	Other/Unknown	no		ADH_Zn_CS, GroES-like_sf, ADH-like_C
SPATA31H1	Other/Unknown	no
CCDC121	Other/Unknown	no		DUF4515
ZNF512	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, ZNF512_znf-C2H2
CDKN2B-AS1	Other/Unknown	no
AIF1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, AIF1/AIF1L
NR2F2-AS1	Other/Unknown	no
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
LAMC3	Other/Unknown	no		Laminin_IV, EGF, LE_dom
MICB	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog

Expression context

Cohort genes with no expression data: 0.

10 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)	12
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	2
ventricular zone	2
granulocyte	2
leukocyte	2
monocyte	2
right lung	2
islet of Langerhans	1
ileal mucosa	1
kidney epithelium	1
right lobe of thyroid gland	1
lower lobe of lung	1
right coronary artery	1
right lobe of liver	1
cardiac muscle of right atrium	1
left ventricle myocardium	1
sperm	1
left testis	1
right testis	1
secondary oocyte	1
cortical plate	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GPN1	297	ubiquitous	marker	islet of Langerhans, ganglionic eminence, ventricular zone
CLPTM1L	255	ubiquitous	marker	ileal mucosa, kidney epithelium, right lobe of thyroid gland
ADH1B	244	broad	marker	right lobe of liver, right coronary artery, lower lobe of lung
SPATA31H1	138	tissue_specific	marker	cardiac muscle of right atrium, left ventricle myocardium, sperm
CCDC121	200	broad	yes	secondary oocyte, right testis, left testis
ZNF512	248	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
CDKN2B-AS1	169	ubiquitous	marker	mucosa of transverse colon, rectum, transverse colon
AIF1	159	broad	marker	monocyte, leukocyte, granulocyte
NR2F2-AS1	188	ubiquitous	marker	sural nerve, left ovary, right ovary
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
LAMC3	184	broad	marker	endocervix, metanephros cortex, right lung
MICB	133	ubiquitous	yes	granulocyte, leukocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AIF1	4,440
GPN1	2,235
ADH1B	2,091
SPATA31H1	1,768
ZNF512	1,624
CLPTM1L	1,606
LAMC3	1,466
CCDC121	492
HLA-DQB1	128
MICB	126

Intra-cohort edges

A	B	Sources
CCDC121	GPN1	string_interaction
CCDC121	SPATA31H1	string_interaction
CCDC121	ZNF512	string_interaction
GPN1	SPATA31H1	string_interaction
GPN1	ZNF512	string_interaction
SPATA31H1	ZNF512	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 5 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DQB1	P01920	10
ADH1B	P00325	9
AIF1	P55008	2
MICB	Q29980	2
ZNF512	Q96ME7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CCDC121	Q6ZUS5	87.88
GPN1	Q9HCN4	79.83
CLPTM1L	Q96KA5	78.54
LAMC3	Q9Y6N6	75.23
SPATA31H1	Q68DN1	34.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 12 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Ethanol oxidation	1	237.9×	0.035	ADH1B
MET promotes cell motility	1	150.3×	0.035	LAMC3
Attachment of bacteria to epithelial cells	1	124.1×	0.035	LAMC3
Laminin interactions	1	95.2×	0.035	LAMC3
MET activates PTK2 signaling	1	95.2×	0.035	LAMC3
Signaling by MET	1	79.3×	0.035	LAMC3
Formation of the dystrophin-glycoprotein complex (DGC)	1	77.2×	0.035	LAMC3
Developmental Lineage of Pancreatic Ductal Cells	1	57.1×	0.038	LAMC3
Phase I - Functionalization of compounds	1	54.9×	0.038	ADH1B
Non-integrin membrane-ECM interactions	1	38.6×	0.049	LAMC3
Biological oxidations	1	32.4×	0.050	ADH1B
Interferon gamma signaling	1	31.4×	0.050	HLA-DQB1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	21.8×	0.066	MICB
Extracellular matrix organization	1	15.8×	0.084	LAMC3
Signaling by Receptor Tyrosine Kinases	1	12.9×	0.095	LAMC3
Adaptive Immune System	1	7.5×	0.151	MICB
Immune System	1	3.2×	0.307	MICB
Metabolism	1	2.9×	0.319	ADH1B
Signal Transduction	1	2.5×	0.339	LAMC3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
immune response-activating cell surface receptor signaling pathway	1	702.2×	0.017	MICB
parallel actin filament bundle assembly	1	702.2×	0.017	AIF1
negative regulation of defense response to virus by host	1	526.6×	0.017	MICB
negative regulation of smooth muscle cell chemotaxis	1	526.6×	0.017	AIF1
positive regulation of smooth muscle cell chemotaxis	1	526.6×	0.017	AIF1
positive regulation of fibroblast growth factor production	1	526.6×	0.017	AIF1
positive regulation of mononuclear cell migration	1	421.3×	0.018	AIF1
constitutive heterochromatin formation	1	300.9×	0.020	ZNF512
gamma-delta T cell activation	1	263.3×	0.020	MICB
adaptive immune response	2	21.1×	0.020	HLA-DQB1, MICB
radial glial cell differentiation	1	191.5×	0.026	LAMC3
ruffle assembly	1	162.0×	0.027	AIF1
actin crosslink formation	1	150.5×	0.027	AIF1
astrocyte development	1	140.4×	0.027	LAMC3
peptide antigen assembly with MHC class II protein complex	1	131.7×	0.027	HLA-DQB1
positive regulation of chemotaxis	1	105.3×	0.030	AIF1
retinoic acid metabolic process	1	100.3×	0.030	ADH1B
positive regulation of monocyte chemotaxis	1	100.3×	0.030	AIF1
positive regulation of T cell migration	1	91.6×	0.030	AIF1
phagocytosis, engulfment	1	84.3×	0.030	AIF1
microglial cell activation	1	78.0×	0.030	AIF1
negative regulation of smooth muscle cell proliferation	1	78.0×	0.030	AIF1
immune response	2	11.8×	0.030	HLA-DQB1, MICB
Rac protein signal transduction	1	70.2×	0.031	AIF1
antigen processing and presentation of exogenous peptide antigen via MHC class II	1	68.0×	0.031	HLA-DQB1
retinoid metabolic process	1	62.0×	0.031	ADH1B
retinol metabolic process	1	62.0×	0.031	ADH1B
actin filament polymerization	1	60.2×	0.031	AIF1
positive regulation of immune response	1	60.2×	0.031	HLA-DQB1
actin filament bundle assembly	1	56.9×	0.031	AIF1

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Cisplatin	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Hydroxyurea	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Dexamethasone, Sintilimab, Thalidomide.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 12

Druggability breadth: 3 of 12 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GPN1	0	0
CLPTM1L	0	0
ADH1B	0	0
SPATA31H1	0	0
CCDC121	0	0
ZNF512	0	0
CDKN2B-AS1	0	0
AIF1	0	0
NR2F2-AS1	0	0
HLA-DQB1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ADH1B	13	Binding:13
CLPTM1L	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	HLA-DQB1, MICB
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	10	GPN1, CLPTM1L, ADH1B, SPATA31H1, CCDC121, ZNF512, CDKN2B-AS1, AIF1, NR2F2-AS1, LAMC3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GPN1	0	—
CLPTM1L	1	—
ADH1B	13	—
SPATA31H1	0	—
CCDC121	0	—
ZNF512	0	—
CDKN2B-AS1	0	—
AIF1	0	—
NR2F2-AS1	0	—
HLA-DQB1	0	—
LAMC3	0	—
MICB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 40.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	23
PHASE2	9
PHASE3	2
PHASE2/PHASE3	2
PHASE1	2
PHASE4	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04265430	PHASE4	RECRUITING	Serial Magnetic Resonance Imaging for the Prediction of Radiation-Induced Changes in Normal Tissue of Patients With Oral Cavity or Skull Base Tumors
NCT05429099	PHASE2/PHASE3	RECRUITING	Mandibular Reconstruction Preplanning (ViPMR)
NCT00359645	PHASE3	COMPLETED	Randomized Trial to Assess the Impact of a Screening Program on Upper Aerodigestive Tract Cancer Mortality in a High Risk Population
NCT00934739	PHASE2/PHASE3	TERMINATED	A Study of High-Risk Oral Cavity Cancer
NCT05369234	PHASE3	COMPLETED	Effects of Oral Aloe Vera Juice on Chemotherapy and Radiation-induced Oral Mucositis and Esophagitis
NCT06728631	PHASE2	ACTIVE_NOT_RECRUITING	Candonilimab and ATRA Acid for Prevention of Oral Cancer Recurrence in Patients With OPL
NCT06876038	PHASE2	NOT_YET_RECRUITING	Low-cost Screening and Image-guided Photodynamic Therapy (PDT) of Premalignant and Malignant Oral Lesions
NCT07063212	PHASE2	RECRUITING	A Study of Sacituzumab Govitecan in Combination With Cetuximab in People With Head and Neck Squamous Cell Cancer (HNSCC)
NCT07209189	PHASE2	RECRUITING	Neoadjuvant Chemotherapy and Programmed Cell Death Protein 1(PD-1) Inhibition for Head and Neck Cancer Treatment De-escalation (NeoScorch HN)
NCT01116843	PHASE1/PHASE2	COMPLETED	Study to Assess Biomarkers in Patients With Resectable Oral Cavity Cancer Randomized to Receive Preoperative Treatment
NCT01695122	PHASE2	COMPLETED	Valproic Acid and Platinum-based Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma
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
NCT04065737	PHASE2	UNKNOWN	Sintilimab to Prevent High-risk Oral Premalignant Lesions Cancerization
NCT04330781	PHASE2	COMPLETED	Radiotherapy of Head and Neck Cancer Using an Intraoral Stent
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
NCT01958762	Not specified	RECRUITING	Screening for Cancers in the Oral CAvity
NCT02012699	Not specified	RECRUITING	Integrated Cancer Repository for Cancer Research
NCT04809324	Not specified	RECRUITING	Gross Examinations Versus Frozen Section for Assessment of Surgical Margins in Oral Cancers
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
NCT05740033	Not specified	RECRUITING	Radial Forearm Donor Site Closure
NCT05757817	Not specified	RECRUITING	Evaluation of the Benefit of a New Surgical Procedure According to IDEAL Recommendations for ORL Cancer Patients: the External Pudendal Flap Used as a New Free Flap for Oral Cavity/Oropharyngeal Reconstruction to Limit Donor Site Sequelae
NCT05793151	Not specified	RECRUITING	Multi-Site Trial of Navigation vs Treatment as Usual to Improve Initiation of Timely Adjuvant Therapy
NCT05798780	Not specified	ACTIVE_NOT_RECRUITING	The ENHANCE Study: Exercise and Nutrition in Head And Neck CancEr Survivors
NCT06407570	Not specified	NOT_YET_RECRUITING	Dysphagia and Quality of Life in Patients With Oral Squamous Cell Carcinoma Before and After Treatment
NCT06806683	Not specified	ACTIVE_NOT_RECRUITING	Predictive Tools in Head and Neck Cancer Patients Undergoing Radiotherapy
NCT07343596	Not specified	RECRUITING	Study to Identify Biomarkers of Oral Cavity Cancer Response to Neoadjuvant Immunotherapy Prior to Definitive Surgery
NCT07606638	Not specified	ENROLLING_BY_INVITATION	Effectiveness of Opioid vs Pregabalin Plus Naproxen Sodium in Pain Management of Oral Cancer Patients
NCT00412490	Not specified	COMPLETED	Smoking Status and Body Image in Oral Cancer Patients
NCT01084733	Not specified	COMPLETED	Nicotine Levels With Response Rates to Radiation Alone or With Chemo In Head & Neck Cancer
NCT02412241	Not specified	COMPLETED	Establishing Lymphedema and Fibrosis Measures in Oral Cancer Patients
NCT02981862	Not specified	COMPLETED	CaptHPV : Validation of the Method CaptHPV for the Diagnosis of Human Papillomavirus Associated Infiltrating Carcinomas
NCT03267914	Not specified	COMPLETED	Impact of Compliance With Fluoride Use on Caries Incidence After Cancer Therapy
NCT03555721	Not specified	TERMINATED	CytID Analysis of Oral Lesions
NCT03942380	Not specified	UNKNOWN	Cell-free Tumor DNA in Head and Neck Cancer Patients
NCT05056064	Not specified	COMPLETED	Efficacy of Swallowing Function After Early Postoperative Oral Exercise Among Patient With Oral Cavity Cancer Underwent Flap Reconstruction
NCT05927220	Not specified	UNKNOWN	WORST PATTERN OF INVASION IN ORAL SQUAMOUS CELL CARCINOMA
NCT06690918	Not specified	COMPLETED	Risk Factors Contributing to Oral Cancer in Patients at Dr. Hasan Sadikin General Hospital Bandung

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CELECOXIB	4	1
DACOMITINIB ANHYDROUS	4	1
NAPROXEN SODIUM	4	1
SACITUZUMAB GOVITECAN	4	1
SUCRALFATE	4	1
THALIDOMIDE	4	1
VALPROIC ACID	4	1
SINTILIMAB	3	1
ZIMBERELIMAB	3	1
ETRUMADENANT	2	1
CHEMBL426123	0	1