Head and neck cancer

Summary

Head and neck cancer (MONDO:0005627) is a cancer (an umbrella term covering 16 Mondo subtypes) with 15 cohort genes (15 GWAS associations across 9 studies; 5 CIViC-evidence somatic drivers; 5 ClinVar predisposition records) and 2,087 clinical trials. Molecularly, PDCD1LG2 EXPRESSION confers sensitivity to Pembrolizumab in Head And Neck Cancer (CIViC Level B); 12 further subtype–drug associations are mapped below. Top therapeutic interventions include docetaxel anhydrous, amifostine, and cisplatin.

At a glance

• Classification: Cancer
• Umbrella term: 16 Mondo subtypes
• Cohort genes: 15
• GWAS associations: 15
• ClinVar variants: 5
• Clinical trials: 2,087
• Precision-medicine evidence (CIViC): 13 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	head and neck cancer
Mondo ID	MONDO:0005627
EFO	EFO:0006859
DOID	DOID:11934
NCIT	C4013
UMLS	C0278996
MedGen	78920
Anatomy (UBERON)	UBERON:0007811
Is cancer (heuristic)	yes

Also known as: cancer of craniocervical region · cancer of head and neck · cancer of the head and neck · craniocervical region cancer · head and neck cancer · head and neck malignant neoplasia · head and neck neoplasm · head and neck tumors · head and neck tumours · head/neck neoplasm · malignant craniocervical region neoplasm · malignant head and neck neoplasm · malignant head and neck tumor · malignant head and neck tumour · malignant neoplasm of craniocervical region · malignant neoplasm of head and neck · malignant neoplasm of the head and neck · malignant tumor of head and neck · malignant tumor of the head and neck · malignant tumour of head and neck (+2 more)

Data availability: 5 ClinVar variants · 15 GWAS associations (9 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 16 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › head and neck cancer

Related subtypes (32): respiratory system cancer, immune system cancer, musculoskeletal system cancer, integumentary system cancer, peritoneum cancer, cardiovascular cancer, reproductive system cancer, malignant giant cell tumor, digestive system cancer, lipomatous cancer, thoracic cancer, malignant glomus tumor, malignant mesenchymoma, carcinoma, sarcoma, blastoma, malignant mixed neoplasm, nervous system cancer, retroperitoneal cancer, malignant germ cell tumor, malignant mesothelioma, malignant urinary system neoplasm, childhood malignant neoplasm, anaplastic cancer, malignant spindle cell neoplasm, high grade malignant neoplasm, malignant endocrine neoplasm, malignant soft tissue neoplasm, secondary malignant neoplasm, refractory malignant neoplasm, malignant adenoma, cancer of unknown primary site

Subtypes (16): nasal cavity cancer, head and neck carcinoma, skull cancer, ocular cancer, malignant cranial nerve neoplasm, malignant ear neoplasm, tongue cancer, cheek mucosa cancer, malignant carotid body paraganglioma, salivary gland cancer, hard palate cancer, gingival cancer, lip cancer, malignant tumor of neck, malignant tumor of floor of mouth, angiosarcoma of the scalp

Genetics & variants

GWAS landscape

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

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12203592	5e-18	IRF4	C	0.26
rs1229984	2e-15	ADH1B	G	1.79
rs3828805	3e-13	HLA-DQB1	C	1.28
rs572923856	6e-13	MCTP1	T	2.94
rs191135255	7e-12	TBC1D1	C	3.28
rs374886195	7e-12	Y_RNA - LINC01896	G	2.15
rs189320201	1e-11	RNU6-248P - RNU6-261P	T	1.9
rs148440552	1e-11	STARP1 - HNRNPA3P5	A	2.86
rs574552866	3e-11	TIAM2	G	4.61
rs183948737	4e-11	ATP6AP1L - RPL5P16	C	1.77
rs79767424	4e-10	RPL32P14 - HSPD1P15	C	1.81
rs1453414	5e-08	TRIM5	C	1.19
rs77452476	3e-07	LAMC3	C	1.24
rs2299187	8e-06	CACNA2D1	A	3.26

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475603	Verma A	2024	4,578	442,171	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST003857	Lesseur C	2016	2,717	5,984	Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
GCST012235	Lesseur C	2016	2,497	2,928	Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
GCST012234	Lesseur C	2016	2,342	2,329	Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
GCST012236	Lesseur C	2016	613	0	Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
GCST90479818	Verma A	2024	492	121,151	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481526	Verma A	2024	492	121,151	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST003541	Azad AK	2016	489	0	A genome-wide association study of non-HPV-related head and neck squamous cell carcinoma identifies prognostic genetic sequence variants in the MAP-kinase and hormone pathways.
GCST90481525	Verma A	2024	233	59,498	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	2
Tier 4: intronic/intergenic	11

MAF distribution

Bucket	Variants
common (>=0.05)	5
low_freq (0.01-0.05)	2
rare (<0.01)	7
unknown	0

Functional consequences

Consequence	Count
intron_variant	8
intergenic_variant	3
regulatory_region_variant	2
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12203592	6	396321	C>G,T	0.16	intron_variant	IRF4	5e-18	Tier 4: intronic/intergenic
rs1229984	4	99318162	T>A,C,G	0.06	missense_variant	ADH1B	2e-15	Tier 1: coding
rs3828805	6	32668343	T>A,C,G	0.28	regulatory_region_variant	HLA-DQB1	3e-13	Tier 3: regulatory
rs572923856	5	94852029	T>A,C	0.001	intron_variant	MCTP1	6e-13	Tier 4: intronic/intergenic
rs191135255	4	37931631	C>A	0	intron_variant	TBC1D1	7e-12	Tier 4: intronic/intergenic
rs374886195	18	78672235	G>A,C,T	0.003	intron_variant	Y_RNA - LINC01896	7e-12	Tier 4: intronic/intergenic
rs189320201	6	76122910	T>C	0.001	intergenic_variant	RNU6-248P - RNU6-261P	1e-11	Tier 4: intronic/intergenic
rs148440552	13	65659024	A>C	0.002	intergenic_variant	STARP1 - HNRNPA3P5	1e-11	Tier 4: intronic/intergenic
rs574552866	6	155122502	G>A,T	0.001	intron_variant	TIAM2	3e-11	Tier 4: intronic/intergenic
rs183948737	5	82755163	C>A	0.002	intergenic_variant	ATP6AP1L - RPL5P16	4e-11	Tier 4: intronic/intergenic
rs79767424	5	19108581	G>A,T	0.03	intron_variant	RPL32P14 - HSPD1P15	4e-10	Tier 4: intronic/intergenic
rs1453414	11	5807854	G>C,T	0.2	regulatory_region_variant	TRIM5	5e-08	Tier 3: regulatory
rs77452476	9	131087186	T>G	0.16	intron_variant	LAMC3	3e-07	Tier 4: intronic/intergenic
rs2299187	7	82417786	C>T	0.02	intron_variant	CACNA2D1	8e-06	Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 not provided, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
813013	NC_000006.12:g.86822028C>A		Uncertain significance	no assertion criteria provided
813016	NC_000022.11:g.20273291G>T		Uncertain significance	no assertion criteria provided
813014	NM_207103.3(SCIMP):c.99T>C (p.Gly33=)	SCIMP	Uncertain significance	no assertion criteria provided
813015	NM_001387274.1(DCDC1):c.247G>A (p.Val83Met)	DCDC1	Benign	criteria provided, multiple submitters, no conflicts
443999	NM_001641.4(APEX1):c.259G>C (p.Glu87Gln)	APEX1	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 41 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
XRCC1			CIViC #6144
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52
MDM2	Act	LMS	CIViC #3465
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
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

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
XRCC1	Limited	Autosomal dominant	head and neck cancer	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MDM2	Orphanet:524	Li-Fraumeni syndrome
MDM2	Orphanet:99970	Dedifferentiated liposarcoma
MDM2	Orphanet:99971	Well-differentiated liposarcoma
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation
PIK3CA	Orphanet:2495	Meningioma
PIK3CA	Orphanet:276280	Hemihyperplasia-multiple lipomatosis syndrome
PIK3CA	Orphanet:295239	Macrodactyly of fingers, unilateral
PIK3CA	Orphanet:295243	Macrodactyly of toes, unilateral
PIK3CA	Orphanet:314662	Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CA	Orphanet:60040	Megalencephaly-capillary malformation-polymicrogyria syndrome
PIK3CA	Orphanet:714737	Diffuse capillary malformation with overgrowth
PIK3CA	Orphanet:90308	Capillary-lymphatic-venous malformation with segmental distribution
PIK3CA	Orphanet:99802	Hemimegalencephaly
PTEN	Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome
PTEN	Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTEN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PTEN	Orphanet:201	Cowden syndrome
PTEN	Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome
PTEN	Orphanet:2969	Proteus-like syndrome
PTEN	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
PTEN	Orphanet:494550	Squamous cell carcinoma of the larynx
PTEN	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTEN	Orphanet:500478	Squamous cell carcinoma of the oropharynx
PTEN	Orphanet:502363	Squamous cell carcinoma of the oral cavity
PTEN	Orphanet:502366	Squamous cell carcinoma of the lip
PTEN	Orphanet:65285	Lhermitte-Duclos disease
PTEN	Orphanet:79076	Juvenile polyposis of infancy
CACNA2D1	Orphanet:130	Brugada syndrome
CACNA2D1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
CACNA2D1	Orphanet:51083	Congenital short QT syndrome
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

15 cohort genes, 15 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	7
civic_only	4
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
XRCC1	HGNC:12828	ENSG00000073050	P18887	DNA repair protein XRCC1	gencc
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
MDM2	HGNC:6973	ENSG00000135679	Q00987	E3 ubiquitin-protein ligase Mdm2	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	civic_evidence
CACNA2D1	HGNC:1399	ENSG00000153956	P54289	Voltage-dependent calcium channel subunit alpha-2/delta-1	gwas
OR52N2	HGNC:15228	ENSG00000180988	Q8NGI0	Olfactory receptor 52N2	gwas
METAP1	HGNC:15789	ENSG00000164024	P53582	Methionine aminopeptidase 1	gwas
DCDC1	HGNC:20625	ENSG00000170959	M0R2J8	Doublecortin domain-containing protein 1	clinvar
ADH1B	HGNC:250	ENSG00000196616	P00325	All-trans-retinol dehydrogenase [NAD(+)] ADH1B	gwas
ADH1C	HGNC:251	ENSG00000248144	P00326	Alcohol dehydrogenase 1C	gwas
SCIMP	HGNC:33504	ENSG00000161929	Q6UWF3	SLP adapter and CSK-interacting membrane protein	clinvar
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
APEX1	HGNC:587	ENSG00000100823	P27695	DNA repair nuclease/redox regulator APEX1	clinvar
LAMC3	HGNC:6494	ENSG00000050555	Q9Y6N6	Laminin subunit gamma-3	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XRCC1	DNA repair protein XRCC1	Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
MDM2	E3 ubiquitin-protein ligase Mdm2	E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome.
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.
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.
CACNA2D1	Voltage-dependent calcium channel subunit alpha-2/delta-1	The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
OR52N2	Olfactory receptor 52N2	Odorant receptor.
METAP1	Methionine aminopeptidase 1	Cotranslationally removes the N-terminal methionine from nascent proteins.
DCDC1	Doublecortin domain-containing protein 1	Microtubule-binding protein which plays an important role in mediating dynein-dependent transport of RAB8A-positive vesicles to the midbody during cytokinesis.
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.
ADH1C	Alcohol dehydrogenase 1C	Alcohol dehydrogenase.
SCIMP	SLP adapter and CSK-interacting membrane protein	Lipid tetraspanin-associated transmembrane adapter/mediator that acts as a scaffold for Src-family kinases and other signaling proteins in immune cells.
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.
APEX1	DNA repair nuclease/redox regulator APEX1	Multifunctional protein that plays a central role in the cellular response to oxidative stress.
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.

Protein-family classification

Druggable: 7 · Difficult: 1 · Unknown: 7 · Druggable fraction: 0.47

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	2	11.2×	0.107
Protease	1	2.4×	0.757
Antibody/Immunoglobulin	1	1.9×	0.757
Kinase	1	1.9×	0.757
GPCR	1	1.6×	0.757
Other/Unknown	7	0.8×	0.856
Enzyme (other)	1	0.8×	0.856
Transcription factor	1	0.6×	0.856

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
XRCC1	Other/Unknown	no		BRCT_dom, Xrcc1_N, Galactose-bd-like_sf
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
MDM2	Transcription factor	no	2.3.2.27	Znf_RING, Znf_RanBP2, SWIB_MDM2_domain
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
CACNA2D1	Other/Unknown	no		VWF_A, VWA_N, VDCC_a2/dsu
OR52N2	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
METAP1	Protease	yes	3.4.11.18	Pept_M24, Pept_M24_MAP, Pept_M24A_MAP1
DCDC1	Other/Unknown	no		Doublecortin_dom, Ricin_B-like_lectins, Doublecortin_dom_sf
ADH1B	Other/Unknown	no		ADH_Zn_CS, GroES-like_sf, ADH-like_C
ADH1C	Enzyme (other)	yes	1.1.1.1	ADH_Zn_CS, GroES-like_sf, ADH-like_C
SCIMP	Other/Unknown	no		SCIMP, Immune_Signaling-Apoptosis_Reg
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
APEX1	Phosphatase	yes	4.2.99.18	AP_endonuc_1, Endo/exonuclease/phosphatase, AP_endonuclease_F1_BS
LAMC3	Other/Unknown	no		Laminin_IV, EGF, LE_dom

Expression context

Cohort genes with no expression data: 0.

14 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)	15
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	4
ventricular zone	3
ganglionic eminence	2
adrenal tissue	2
granulocyte	2
male germ line stem cell (sensu Vertebrata) in testis	2
right lung	2
tendon of biceps brachii	1
sural nerve	1
tibia	1
tendon	1
endothelial cell	1
sperm	1
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
islet of Langerhans	1
epithelium of esophagus	1
esophagus squamous epithelium	1
left testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
XRCC1	276	ubiquitous	marker	ventricular zone, tendon of biceps brachii, ganglionic eminence
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
MDM2	274	ubiquitous	marker	calcaneal tendon, adrenal tissue, ventricular zone
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
CACNA2D1	261	ubiquitous	marker	biceps brachii, skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis
OR52N2	33		yes	male germ line stem cell (sensu Vertebrata) in testis, granulocyte, islet of Langerhans
METAP1	293	ubiquitous	marker	esophagus squamous epithelium, left testis, epithelium of esophagus
DCDC1	148	broad	marker	oviduct epithelium, right uterine tube, male germ line stem cell (sensu Vertebrata) in testis
ADH1B	244	broad	marker	right lobe of liver, right coronary artery, lower lobe of lung
ADH1C	199	tissue_specific	marker	mucosa of transverse colon, jejunal mucosa, nasal cavity epithelium
SCIMP	133	broad	marker	monocyte, leukocyte, granulocyte
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
APEX1	294	ubiquitous	marker	ganglionic eminence, embryo, ventricular zone
LAMC3	184	broad	marker	endocervix, metanephros cortex, right lung

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTEN	11,626
MDM2	9,892
PIK3CA	5,157
APEX1	5,100
METAP1	4,378
SLTM	2,598
XRCC1	2,591
ADH1B	2,091
CACNA2D1	2,002
ADH1C	1,955

Intra-cohort edges

A	B	Sources
ADH1B	ADH1C	biogrid_interaction, intact
ADH1B	OR52N2	string_interaction
APEX1	XRCC1	biogrid_interaction, intact, string_interaction
LAMC3	OR52N2	string_interaction
PIK3CA	PTEN	string_interaction
PIK3CA	SLTM	intact

Structural data

PDB: 10 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MDM2	Q00987	147
PIK3CA	P42336	135
APEX1	P27695	67
METAP1	P53582	41
CACNA2D1	P54289	30
XRCC1	P18887	13
PTEN	P60484	12
HLA-DQB1	P01920	10
ADH1B	P00325	9
ADH1C	P00326	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OR52N2	Q8NGI0	89.62
LAMC3	Q9Y6N6	75.23
DCDC1	M0R2J8	68.53
SCIMP	Q6UWF3	66.71
SLTM	Q9NWH9	52.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 154. Enrichment computed across 15 evidence-associated genes (12 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 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Resolution of AP sites via the single-nucleotide replacement pathway	2	380.7×	0.002	XRCC1, APEX1
Ethanol oxidation	2	158.6×	0.005	ADH1B, ADH1C
Phase I - Functionalization of compounds	2	36.6×	0.054	ADH1B, ADH1C
Synthesis of PIPs at the plasma membrane	2	35.2×	0.054	PIK3CA, PTEN
PTEN Loss of Function in Cancer	1	475.8×	0.054	PTEN
Abasic sugar-phosphate removal via the single-nucleotide replacement pathway	1	317.2×	0.054	APEX1
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1	237.9×	0.054	APEX1
MET activates PI3K/AKT signaling	1	158.6×	0.054	PIK3CA
Activated NTRK3 signals through PI3K	1	158.6×	0.054	PIK3CA
APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway	1	135.9×	0.054	XRCC1
Activated NTRK2 signals through PI3K	1	135.9×	0.054	PIK3CA
Signaling by LTK in cancer	1	135.9×	0.054	PIK3CA
POLB-Dependent Long Patch Base Excision Repair	1	105.7×	0.054	APEX1
PI3K/AKT activation	1	105.7×	0.054	PIK3CA
The phototransduction cascade	1	105.7×	0.054	METAP1
Resolution of Abasic Sites (AP sites)	1	95.2×	0.054	APEX1
Regulation of PTEN mRNA translation	1	95.2×	0.054	PTEN
Displacement of DNA glycosylase by APEX1	1	86.5×	0.054	APEX1
IRS-mediated signalling	1	86.5×	0.054	PIK3CA
PI3K events in ERBB4 signaling	1	86.5×	0.054	PIK3CA
Regulation of PTEN localization	1	86.5×	0.054	PTEN
Co-stimulation by ICOS	1	86.5×	0.054	PIK3CA
Signaling by FGFR4 in disease	1	79.3×	0.054	PIK3CA
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	79.3×	0.054	PIK3CA
HDR through MMEJ (alt-NHEJ)	1	73.2×	0.054	XRCC1
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	73.2×	0.054	PIK3CA
Signaling by PDGFRA extracellular domain mutants	1	73.2×	0.054	PIK3CA
Signaling by LTK	1	73.2×	0.054	PIK3CA
AKT phosphorylates targets in the cytosol	1	68.0×	0.054	MDM2
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	63.4×	0.054	MDM2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to muscle inactivity	1	1203.7×	0.025	PIK3CA
cellular response to vitamin B1	1	1203.7×	0.025	MDM2
response to butyrate	1	1203.7×	0.025	PIK3CA
response to formaldehyde	1	1203.7×	0.025	MDM2
negative regulation of protein ADP-ribosylation	1	601.9×	0.025	XRCC1
telomere maintenance via base-excision repair	1	601.9×	0.025	APEX1
regulation of base-excision repair	1	601.9×	0.025	XRCC1
negative regulation of synaptic vesicle clustering	1	601.9×	0.025	PTEN
toll-like receptor TLR1:TLR2 signaling pathway	1	401.2×	0.025	SCIMP
response to L-leucine	1	401.2×	0.025	PIK3CA
response to ether	1	401.2×	0.025	MDM2
negative regulation of keratinocyte migration	1	401.2×	0.025	PTEN
calcium ion transmembrane transport via high voltage-gated calcium channel	1	401.2×	0.025	CACNA2D1
cellular response to hydrostatic pressure	1	401.2×	0.025	PIK3CA
membrane depolarization during bundle of His cell action potential	1	401.2×	0.025	CACNA2D1
regulation of membrane repolarization during action potential	1	401.2×	0.025	CACNA2D1
regulation of mitotic cytokinesis	1	401.2×	0.025	DCDC1
response to water-immersion restraint stress	1	401.2×	0.025	MDM2
retinoic acid metabolic process	2	114.6×	0.025	ADH1B, ADH1C
retinol metabolic process	2	70.8×	0.025	ADH1B, ADH1C
base-excision repair	2	66.9×	0.025	XRCC1, APEX1
negative regulation of neuron projection development	2	33.9×	0.025	MDM2, PTEN
phosphatidylinositol 3-kinase/protein kinase B signal transduction	2	30.1×	0.025	PIK3CA, PTEN
traversing start control point of mitotic cell cycle	1	300.9×	0.027	MDM2
rhythmic synaptic transmission	1	300.9×	0.027	PTEN
telomeric DNA-containing double minutes formation	1	300.9×	0.027	XRCC1
cellular response to molecule of fungal origin	1	300.9×	0.027	SCIMP
regulation of protein catabolic process at postsynapse, modulating synaptic transmission	1	300.9×	0.027	MDM2
negative regulation of protection from non-homologous end joining at telomere	1	300.9×	0.027	XRCC1
positive regulation of dendritic cell cytokine production	1	240.7×	0.029	SCIMP

Therapeutics

Drugs indicated for this disease

3 approved, 39 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Amifostine	Approved (phase 4)
Cetuximab	Approved (phase 4)
Temoporfin	Approved (phase 4)
Afatinib	Phase 3 (in late-stage trials)
Aldesleukin	Phase 3 (in late-stage trials)
Buparlisib	Phase 3 (in late-stage trials)
Capsaicin	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Dostarlimab	Phase 3 (in late-stage trials)
Epacadostat	Phase 3 (in late-stage trials)
Epoetin Alfa	Phase 3 (in late-stage trials)
Erlotinib	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Gabapentin	Phase 3 (in late-stage trials)
Gefitinib	Phase 3 (in late-stage trials)
Gimeracil	Phase 3 (in late-stage trials)
Interferon Alfa	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Isotretinoin	Phase 3 (in late-stage trials)
Lapatinib	Phase 3 (in late-stage trials)
Linrodostat	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Mitomycin	Phase 3 (in late-stage trials)
Nimotuzumab	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Oteracil	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Palifermin	Phase 3 (in late-stage trials)
Panitumumab	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Pemetrexed	Phase 3 (in late-stage trials)
Porfiromycin	Phase 3 (in late-stage trials)
St. John’S Wort	Phase 3 (in late-stage trials)
Tegafur	Phase 3 (in late-stage trials)
Thyrotropin	Phase 3 (in late-stage trials)
Uracil	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)
Xevinapant	Phase 3 (in late-stage trials)
Zalutumumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Amoxicillin, Atezolizumab, Bempegaldesleukin, Bevacizumab, Bleomycin, Bortezomib, Cabazitaxel, Capecitabine, Clavulanic Acid, Cyanocobalamin, Durvalumab, Epoetin Beta, Everolimus, Fenretinide, Figitumumab, Folic Acid, Gemcitabine, Honey, Hydroxyurea, Ibrutinib, Irinotecan, Linsitinib, Megestrol Acetate, Melatonin, Minocycline, Niraparib, Nogapendekin Alfa, Omeprazole, Oxaliplatin, PEGINTERFERON ALFA-2B, Pegfilgrastim, Penicillamine, Perifosine, Plerixafor, Porfimer Sodium, Pralatrexate, Rebamipide, Retifanlimab, Rivoceranib, Sodium Chloride, Surufatinib, Thalidomide, Tislelizumab, Toripalimab, Trastuzumab, Urea, Valproic Acid, Vandetanib.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 9

Druggability breadth: 11 of 15 evidence-associated genes (73%) 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
SLTM	CABOZANTINIB
MDM2	NITROFURANTOIN
PIK3CA	IDELALISIB
CACNA2D1	PREGABALIN
METAP1	CLIOQUINOL
APEX1	CEFOTAXIME SODIUM

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIK3CA	67	4
APEX1	53	4
MDM2	14	4
CACNA2D1	5	4
METAP1	4	4
SLTM	1	4
XRCC1	0	0
PTEN	0	0
OR52N2	0	0
DCDC1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CABOZANTINIB	4	SLTM
NITROFURANTOIN	4	MDM2
APOMORPHINE	4	MDM2
CYTARABINE	4	MDM2
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
BELINOSTAT	4	PIK3CA
INAVOLISIB	4	PIK3CA
SUNITINIB	4	PIK3CA
DASATINIB	4	PIK3CA
CRIZOTINIB	4	PIK3CA
MIDOSTAURIN	4	PIK3CA
PREGABALIN	4	CACNA2D1
GABAPENTIN	4	CACNA2D1
NIMODIPINE	4	CACNA2D1
TACRINE	4	CACNA2D1
CLIOQUINOL	4	METAP1
THIABENDAZOLE	4	METAP1
CEFOTAXIME SODIUM	4	APEX1
IDARUBICIN	4	APEX1
DECAMETHONIUM BROMIDE	4	APEX1
ROPINIROLE HYDROCHLORIDE	4	APEX1
AVOBENZONE	4	APEX1
CYCLOBENZAPRINE HYDROCHLORIDE	4	APEX1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
MDM2	1,007	Binding:979, Functional:28
METAP1	79	Binding:75, ADMET:4
APEX1	49	Binding:45, Functional:4
CACNA2D1	47	Binding:45, ADMET:1, Toxicity:1
SLTM	14	Binding:14
ADH1B	13	Binding:13
ADH1C	12	Binding:12
PTEN	8	Binding:8
SCIMP	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MDM2	2.3.2.27	RING-type E3 ubiquitin transferase
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
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
METAP1	3.4.11.18	methionyl aminopeptidase
ADH1C	1.1.1.1	alcohol dehydrogenase
APEX1	4.2.99.18	DNA-(apurinic or apyrimidinic site) lyase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MDM2	1,007
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 15; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

29 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)
CABOZANTINIB	4	SLTM
NITROFURANTOIN	4	MDM2
APOMORPHINE	4	MDM2
CYTARABINE	4	MDM2
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
BELINOSTAT	4	PIK3CA
INAVOLISIB	4	PIK3CA
SUNITINIB	4	PIK3CA
DASATINIB	4	PIK3CA
CRIZOTINIB	4	PIK3CA
MIDOSTAURIN	4	PIK3CA
PREGABALIN	4	CACNA2D1
NIMODIPINE	4	CACNA2D1
TACRINE	4	CACNA2D1
CLIOQUINOL	4	METAP1
THIABENDAZOLE	4	METAP1
CEFOTAXIME SODIUM	4	APEX1
IDARUBICIN	4	APEX1
DECAMETHONIUM BROMIDE	4	APEX1
ROPINIROLE HYDROCHLORIDE	4	APEX1
AVOBENZONE	4	APEX1
CYCLOBENZAPRINE HYDROCHLORIDE	4	APEX1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	SLTM, MDM2, PIK3CA, CACNA2D1, METAP1, APEX1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	PTEN, ADH1C, HLA-DQB1
D	Druggable family + AlphaFold only, no drug	1	OR52N2
E	Difficult family or no structure, no drug	5	XRCC1, DCDC1, ADH1B, SCIMP, LAMC3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
XRCC1	0	APEX1
PTEN	8	—
OR52N2	0	—
DCDC1	0	—
ADH1B	13	—
ADH1C	12	—
SCIMP	1	—
HLA-DQB1	0	—
LAMC3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,087.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	477
PHASE1	256
PHASE3	137
PHASE1/PHASE2	134
EARLY_PHASE1	41
PHASE4	34
PHASE2/PHASE3	21

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06521697	PHASE4	NOT_YET_RECRUITING	Effects of Minimal-Flow Sevoflurane and Multimodal Analgesia in Head and Neck Cancer Surgery
NCT06734598	PHASE4	RECRUITING	Efficacy of Botox Injection of the Masticatory Muscles in Head &Neck Cancer Patients with Trismus After Radiotherapy
NCT06807034	PHASE4	ACTIVE_NOT_RECRUITING	Impact of the Oral Microbiota on Relapse in HNSCC Patients
NCT06879691	PHASE4	ACTIVE_NOT_RECRUITING	A Trial of Nimotuzumab and Pinkiller Efficacy and Pain in Advanced Head and Neck Squamous Cell Carcinoma
NCT07158164	PHASE4	RECRUITING	DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
NCT07189897	PHASE4	RECRUITING	Apixaban or Enoxaparin After Head and Neck Cancer Surgery
NCT00138827	PHASE4	COMPLETED	Mouth Care Regimes During Radiotherapy
NCT00158041	PHASE4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00198263	PHASE4	COMPLETED	Study Using the Medpulser Electroporation System With Bleomycin to Treat Head and Neck Cancer
NCT00333099	PHASE4	COMPLETED	INEC Study: Immuno-modulating Enteral Nutrition in Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00772681	PHASE4	COMPLETED	Efficacy of Chemoradiotherapy After Neoadjuvant Cisplatin and Docetaxel in the Nasopharynx Carcinoma
NCT00813631	PHASE4	UNKNOWN	The Effect on an Ionic Silver Dressing in Head and Neck Patients With Malignant Fungating Wound
NCT01317589	PHASE4	COMPLETED	Treatment of Pain in Head-and-Neck Cancer Patients: is Methadone More Effective?
NCT01418118	PHASE4	COMPLETED	Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery
NCT01553032	PHASE4	COMPLETED	Skin Changes in Head and Neck Cancer During Immuno-(Chemo-) And Radiotherapy With Erbitux® (HICARE)
NCT02015650	PHASE4	TERMINATED	Cetuximab Compared to Mitomycin-C and 5-Fluorouracil for Locally Advanced Squamous Cell Carcinomas of the Head and Neck
NCT02049112	PHASE4	COMPLETED	A New Oral salIvary equivAlent Compared to Two moisturizinG Mouth sprAys in Patients With xeRostomiA: NIAGARA Study
NCT02241083	PHASE4	COMPLETED	The Effect of Norepinephrine and Dopamine on Radial Forearm Free Flap Tissue Oxygen Pressure and Microdialysate Metabolite Measurements
NCT02241876	PHASE4	UNKNOWN	THE USE OF N-ACETYLCYSTEINE ATTENUATING CISPLATIN-INDUCED TOXICITIES BY OXIDATIVE STRESS
NCT02597582	PHASE4	COMPLETED	LigaSure Small Jaw® Versus Conventional Neck Dissection in Head and Neck Cancer Patients
NCT02622880	PHASE4	COMPLETED	Comparison of Two Immunomodulatory Formulas on the Number of Postoperative Infections in Head & Neck Cancer Patients
NCT02880072	PHASE4	COMPLETED	Absorption of Orally Ingested Phosphate in Refeeding Syndrome
NCT02926573	PHASE4	COMPLETED	Perioperative Gabapentin Use In Head And Neck Mucosal Surgery Patients
NCT03607227	PHASE4	COMPLETED	Continous Popliteal Block for Microvascular Free Flap Reconstruction in Ear, Nose and Throat Surgery
NCT03714867	PHASE4	WITHDRAWN	Pre-Operative Pregabalin for Post-Operative Pain in Head and Neck Cancer Surgery
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04246697	PHASE4	COMPLETED	Multimodal Pain Study in Free Flap Patients
NCT04292990	PHASE4	UNKNOWN	Comparison of Transdermal Fentanyl and Morphine for Oral Mucositis Pain in Nasopharyngeal Cancer Patients
NCT04507035	PHASE4	UNKNOWN	Treating Locally Advanced Head and Neck Malignant Tumor With Anlotinib and Chemoradiotherapy
NCT04977271	PHASE4	WITHDRAWN	Mood Disorders in Head and Neck Cancer Patients
NCT05046028	PHASE4	COMPLETED	Individualization of Nutritive Sensory Support Of Radiation Therapy
NCT05055726	PHASE4	COMPLETED	Benzydamine Oromucosal Solution in Oral Mucositis (BOOM)
NCT00956007	PHASE3	ACTIVE_NOT_RECRUITING	RT With or Without Cetuximab in Treating Patients Who Have Undergone Surgery for Locally Advanced Head and Neck Cancer
NCT01266044	PHASE3	ACTIVE_NOT_RECRUITING	Controlled Trial Of Acupuncture To Prevent Radiation-Induced Xerostomia
NCT03755739	PHASE2/PHASE3	RECRUITING	Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors
NCT03765918	PHASE3	ACTIVE_NOT_RECRUITING	Study of Pembrolizumab Given Prior to Surgery and in Combination With Radiotherapy Given Post-surgery for Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-689)
NCT03769506	PHASE3	ACTIVE_NOT_RECRUITING	ASP-1929 Photoimmunotherapy (PIT) Study in Recurrent Head/Neck Cancer for Patients Who Have Failed at Least Two Lines of Therapy
NCT03840421	PHASE3	ACTIVE_NOT_RECRUITING	GP Vs PF As Induction Chemotherapy Combined with CCRT for Locoregionally Advanced Nasopharyngeal Carcinoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DOCETAXEL ANHYDROUS	4	24
AMIFOSTINE	4	14
CISPLATIN	4	14
CETUXIMAB	4	13
FLUOROURACIL	4	11
EVEROLIMUS	4	10
AFATINIB	4	9
HYDROXYUREA	4	6
INDOCYANINE GREEN ACID FORM	4	6
PANITUMUMAB	4	6
VENLAFAXINE	4	6
ERLOTINIB	4	5
PALIFERMIN	4	5
RETIFANLIMAB	4	5
NIVOLUMAB	4	4
PEMBROLIZUMAB	4	4
SARGRAMOSTIM	4	4
ABEMACICLIB	4	3
CEMIPLIMAB	4	3
DOSTARLIMAB	4	3
GEFITINIB	4	3
NIRAPARIB	4	3
VANDETANIB	4	3
ALDESLEUKIN	4	2
ARMODAFINIL	4	2
CLOPIDOGREL BISULFATE	4	2
EPOETIN ALFA	4	2
GABAPENTIN	4	2
GEMCITABINE HYDROCHLORIDE	4	2
GLUTAMINE	4	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 13 predictive associations from 14 curated evidence items; also 3 oncogenic, 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
PDCD1LG2 EXPRESSION	Pembrolizumab	Sensitivity/Response	CIViC B	EID5917
DEK::AFF2 Fusion	Pembrolizumab	Sensitivity/Response	CIViC C	EID7304
FGFR1::PLAG1 Fusion	Futibatinib	Sensitivity/Response	CIViC C	EID11639
MET R1004G	Crizotinib	Sensitivity/Response	CIViC C	EID7498
PIK3CA H1047R	Dactolisib	Sensitivity/Response	CIViC D	EID1361 +1
NBN Loss	GPI-15427	Sensitivity/Response	CIViC D	EID1954
PIK3CA H1047R	Cetuximab + Dactolisib	Sensitivity/Response	CIViC D	EID1363
PIK3CA H1047R	Alpelisib	Sensitivity/Response	CIViC D	EID1401
PIK3CA Mutation	Dactolisib	Sensitivity/Response	CIViC D	EID1360
PIK3CA Mutation	Trametinib + Pictilisib + Tanespimycin	Sensitivity/Response	CIViC D	EID1364
PTEN Mutation	Tanespimycin + Pictilisib	Sensitivity/Response	CIViC D	EID1359
HRAS G12D	Erlotinib	Resistance	CIViC D	EID3697
HRAS G12V	Erlotinib	Resistance	CIViC D	EID3854