Head and neck squamous cell carcinoma

Summary

Head and neck squamous cell carcinoma (MONDO:0010150) is a cancer (an umbrella term covering 13 Mondo subtypes) with 28 cohort genes (6 GWAS associations across 3 studies; 24 CIViC-evidence somatic drivers; 62 ClinVar predisposition records) and 1,051 clinical trials. The dominant Reactome pathway is RAF/MAP kinase cascade (12 cohort genes). Molecularly, CDKN1B EXPRESSION confers sensitivity to Cisplatin + Fluorouracil in Head And Neck Squamous Cell Carcinoma (CIViC Level B); 42 further subtype–drug associations are mapped below. Top therapeutic interventions include cisplatin, cetuximab, and tremelimumab.

At a glance

• Classification: Cancer
• Umbrella term: 13 Mondo subtypes
• Cohort genes: 28
• GWAS associations: 6
• ClinVar variants: 62
• Clinical trials: 1,051
• Precision-medicine evidence (CIViC): 43 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	head and neck squamous cell carcinoma
Mondo ID	MONDO:0010150
EFO	EFO:0000181
MeSH	C535575
OMIM	275355
Orphanet	67037
DOID	DOID:5520
NCIT	C34447
SNOMED CT	716659002
UMLS	C1168401
MedGen	257911
GARD	0008503
MedDRA	10060121
Anatomy (UBERON)	UBERON:0007811
Is cancer (heuristic)	yes

Also known as: carcinoma of the head and neck · craniocervical region squamous cell carcinoma · head and neck squamous cell carcinoma · HNSCC · SCCHN · squamous cell carcinoma of head and neck · squamous cell carcinoma of the head and neck · squamous cell carcinoma, head and neck · squamous cell carcinoma, head and neck, somatic

Data availability: 62 ClinVar variants · 6 GWAS associations (3 studies) · 4 GenCC gene-disease records · 97 cell lines · 72 intOGen driver records.

Disease family

An umbrella term covering 13 Mondo subtypes.

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

Related subtypes (15): eye carcinoma, external ear carcinoma, middle ear carcinoma, nasal cavity carcinoma, growth hormone-producing pituitary gland carcinoma, hypopharyngeal carcinoma, ameloblastic carcinoma, laryngeal small cell carcinoma, pharyngeal adenoid cystic carcinoma, nasopharyngeal carcinoma, pituitary adenocarcinoma, carcinoma of floor of mouth, lip and oral cavity carcinoma, oropharyngeal carcinoma, nasal cavity and paranasal sinus carcinoma

Subtypes (13): pharyngeal squamous cell carcinoma, cornea squamous cell carcinoma, lacrimal gland squamous cell carcinoma, external ear squamous cell carcinoma, laryngeal squamous cell carcinoma, nasal cavity squamous cell carcinoma, nasopharyngeal squamous cell carcinoma, conjunctival squamous cell carcinoma, middle ear squamous cell carcinoma, primary intraosseous squamous cell carcinoma, paranasal sinus squamous cell carcinoma, lip and oral cavity squamous cell carcinoma, nasal cavity and paranasal sinus squamous cell carcinoma

Genetics & variants

GWAS landscape

6 GWAS associations across 3 studies. Top hits map to 6 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs671	1e-25	ALDH2	?
rs3135001	1e-16	HLA-DQB1 - MTCO3P1	C	1.3
rs1265081	4e-10	CCHCR1	A	1.18
rs259919	3e-09	POLR1HASP, POLR1HASP	A	1.17
rs16879870	4e-06	RN7SL643P - HTR1E	?	2.02
rs2641256	8e-06	SCIMP, ZNF594-DT	?	1.49

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010288	Shete S	2020	2,171	4,493	A genome-wide association study identifies two novel susceptible regions for squamous cell carcinoma of the head and neck.
GCST90428466	Chien HT	2023	697	2,388	Single-nucleotide polymorphism at alcohol dehydrogenase 1B: A susceptible gene marker in oro-/hypopharyngeal cancers from genome-wide association study.
GCST009985	He Y	2020	261	0	Genetic Variants Were Associated With the Prognosis of Head and Neck Squamous Carcinoma.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	6
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	2
missense_variant	1
intergenic_variant	1
splice_polypyrimidine_tract_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs671	12	111803962	G>A	0.05	missense_variant	ALDH2	1e-25	Tier 1: coding
rs3135001	6	32702359	T>A,C	0.21	intergenic_variant	HLA-DQB1 - MTCO3P1	1e-16	Tier 4: intronic/intergenic
rs1265081	6	31143898	C>A	0.48	intron_variant	CCHCR1	4e-10	Tier 4: intronic/intergenic
rs259919	6	30057726	G>A,C,T	0.28	splice_polypyrimidine_tract_variant	POLR1HASP, POLR1HASP	3e-09	Tier 2: splice/UTR
rs16879870	6	86822028	C>A	0.05	intron_variant	RN7SL643P - HTR1E	4e-06	Tier 4: intronic/intergenic
rs2641256	17	5223379	A>G	0.05	synonymous_variant	SCIMP, ZNF594-DT	8e-06	Tier 4: intronic/intergenic

ClinVar germline variants

62 retrieved; paginated sample, class counts are floors:

13 pathogenic, 9 conflicting classifications of pathogenicity, 9 benign/likely benign, 8 likely benign, 7 pathogenic/likely pathogenic, 5 uncertain significance, 4 drug response, 3 benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic/pathogenic, low penetrance, 1 likely pathogenic; drug response

ClinVar	Variant (HGVS)	Gene	Classification	Review
8067	NM_198219.3(ING1):c.644G>C (p.Cys215Ser)	ING1	Pathogenic	no assertion criteria provided
8068	NM_198219.3(ING1):c.647A>G (p.Asn216Ser)	ING1	Pathogenic	no assertion criteria provided
8069	NM_198219.3(ING1):c.575C>A (p.Ala192Asp)	ING1	Pathogenic	no assertion criteria provided
6194	NM_003842.5(TNFRSF10B):c.1150_1151dup (p.Met385fs)	TNFRSF10B	Pathogenic	no assertion criteria provided
12352	NM_000546.6(TP53):c.747G>T (p.Arg249Ser)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12364	NM_000546.6(TP53):c.844C>T (p.Arg282Trp)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12366	NM_000546.6(TP53):c.818G>A (p.Arg273His)	TP53	Pathogenic	reviewed by expert panel
12374	NM_000546.6(TP53):c.524G>A (p.Arg175His)	TP53	Pathogenic	reviewed by expert panel
12379	NM_000546.6(TP53):c.1010G>A (p.Arg337His)	TP53	Pathogenic/Likely pathogenic/Pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
127819	NM_000546.6(TP53):c.659A>G (p.Tyr220Cys)	TP53	Pathogenic	reviewed by expert panel
142320	NM_000546.6(TP53):c.542G>A (p.Arg181His)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142766	NM_000546.6(TP53):c.455C>T (p.Pro152Leu)	TP53	Pathogenic	reviewed by expert panel
161516	NM_000546.6(TP53):c.797G>A (p.Gly266Glu)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182930	NM_000546.6(TP53):c.493C>T (p.Gln165Ter)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
184979	NM_000546.6(TP53):c.578A>G (p.His193Arg)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
246118	NM_000546.6(TP53):c.473G>C (p.Arg158Pro)	TP53	Pathogenic	reviewed by expert panel
376659	NM_000546.6(TP53):c.845G>C (p.Arg282Pro)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
43590	NM_000546.6(TP53):c.637C>T (p.Arg213Ter)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
584921	NM_000546.6(TP53):c.718A>G (p.Ser240Gly)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
659670	NM_000546.6(TP53):c.383del (p.Pro128fs)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
803307	NM_000546.6(TP53):c.713dup (p.Cys238fs)	TP53	Pathogenic	criteria provided, single submitter
45224	NM_005228.5(EGFR):c.2155G>C (p.Gly719Arg)	EGFR	Likely pathogenic; drug response	no assertion criteria provided
3067904	NM_003842.5(TNFRSF10B):c.598del (p.Ser200fs)	TNFRSF10B	Likely pathogenic	criteria provided, single submitter
376624	NM_000546.6(TP53):c.396G>C (p.Lys132Asn)	TP53	Likely pathogenic	reviewed by expert panel
126517	NM_005228.5(EGFR):c.2471G>A (p.Gly824Asp)	EGFR	drug response	no assertion criteria provided
126518	NM_005228.5(EGFR):c.2188C>G (p.Leu730Val)	EGFR	drug response	no assertion criteria provided
126519	NM_005228.5(EGFR):c.2393T>A (p.Leu798His)	EGFR	drug response	no assertion criteria provided
126520	NM_005228.5(EGFR):c.2176G>A (p.Val726Met)	EGFR	drug response	no assertion criteria provided
126515	NM_005228.5(EGFR):c.2327G>A (p.Arg776His)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161397	NM_000546.6(TP53):c.665C>T (p.Pro222Leu)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 144 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
EGFR	Act	BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC	CIViC #19
ING1	LoF	COADREAD,UCEC
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
TGFA			CIViC #5742
ALDH1A2			CIViC #7024
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
CD274	LoF	DLBCLNOS	CIViC #11335
CDKN1B	LoF	BRCA,HCC,PCM,PRAD,SIC	CIViC #914
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
DPYD			CIViC #1526
EGF			CIViC #1634
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
FGFR1	Act	BLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTC	CIViC #1885
FGFR2	Act	BRCA,CHOL,LUSC,SACA,UCEC	CIViC #22
HRAS	Act	ANGS,BLCA,BRCA,COADREAD,CSCC,HNSC,LUSC,NPC,PGNG,PRAD,PROSTATE,THYM,UTUC,WDTC	CIViC #2747
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
AREG			CIViC #389
SMAD4	LoF	BRCA,CESC,CHOL,COAD,COADREAD,ESCA,ESCC,GBC,HNSC,LUAD,NSCLC,PAAD,PANCREAS,PRAD,PROSTATE,READ,STAD,STOMACH	CIViC #77
MAPK1	Act	CESC,CLLSLL,HCC,HNSC	CIViC #4532
NOTCH1	LoF	ALL,ANGS,BCC,BLCA,BRCA,CESC,CHOL,CLLSLL,CSCC,DLBCLNOS,ESCA,HNSC,LGGNOS,LUAD,LUSC,MBL,MEL,MGCT,NPC,NSCLC,OVT,READ,SACA,SCLC,SKIN,VULVA	CIViC #50
NRG1	Act	ESCA,PRCC,STAD	CIViC #2593
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
PTPRT	Act	ESCA,HCC,HNSC,MEL,OVT,PAAD,STAD	CIViC #8878

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
TNFRSF10B	Limited	Autosomal dominant	head and neck squamous cell carcinoma	3
ING1	No Known Disease Relationship	Unknown	head and neck squamous cell carcinoma

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNFRSF10B	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
TNFRSF10B	Orphanet:494550	Squamous cell carcinoma of the larynx
TNFRSF10B	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
TNFRSF10B	Orphanet:500478	Squamous cell carcinoma of the oropharynx
TNFRSF10B	Orphanet:502363	Squamous cell carcinoma of the oral cavity
TNFRSF10B	Orphanet:502366	Squamous cell carcinoma of the lip
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
ING1	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
ING1	Orphanet:494550	Squamous cell carcinoma of the larynx
ING1	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
ING1	Orphanet:500478	Squamous cell carcinoma of the oropharynx
ING1	Orphanet:502363	Squamous cell carcinoma of the oral cavity
ING1	Orphanet:502366	Squamous cell carcinoma of the lip
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
TGFA	Orphanet:99798	Oligodontia
CCND1	Orphanet:29073	Multiple myeloma

Cohort genes → proteins

28 cohort genes, 27 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	3
civic_only	20
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNFRSF10B	HGNC:11905	ENSG00000120889	O14763	Tumor necrosis factor receptor superfamily member 10B	gencc,clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	clinvar,civic_evidence
ING1	HGNC:6062	ENSG00000153487	Q9UK53	Inhibitor of growth protein 1	gencc,clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar,civic_evidence
TGFA	HGNC:11765	ENSG00000163235	P01135	Protransforming growth factor alpha	civic_evidence
ALDH1A2	HGNC:15472	ENSG00000128918	O94788	Retinal dehydrogenase 2	civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	civic_evidence
CD274	HGNC:17635	ENSG00000120217	Q9NZQ7	Programmed cell death 1 ligand 1	civic_evidence
CDKN1B	HGNC:1785	ENSG00000111276	P46527	Cyclin-dependent kinase inhibitor 1B	civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	civic_evidence
DPYD	HGNC:3012	ENSG00000188641	Q12882	Dihydropyrimidine dehydrogenase [NADP(+)]	civic_evidence
EGF	HGNC:3229	ENSG00000138798	P01133	Pro-epidermal growth factor	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	civic_evidence
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
AREG	HGNC:651	ENSG00000109321	P15514	Amphiregulin	civic_evidence
SMAD4	HGNC:6770	ENSG00000141646	Q13485	SMAD family member 4	civic_evidence
MAPK1	HGNC:6871	ENSG00000100030	P28482	Mitogen-activated protein kinase 1	civic_evidence
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	civic_evidence
NRG1	HGNC:7997	ENSG00000157168	Q02297	Pro-neuregulin-1, membrane-bound isoform	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
PTPRT	HGNC:9682	ENSG00000196090	O14522	Receptor-type tyrosine-protein phosphatase T	civic_evidence
POLR1HASP	HGNC:13924	ENSG00000204623		POLR1H antisense, pseudogene	gwas
CCHCR1	HGNC:13930	ENSG00000204536	Q8TD31	Coiled-coil alpha-helical rod protein 1	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNFRSF10B	Tumor necrosis factor receptor superfamily member 10B	Receptor for the cytotoxic ligand TNFSF10/TRAIL.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
ING1	Inhibitor of growth protein 1	Cooperates with p53/TP53 in the negative regulatory pathway of cell growth by modulating p53-dependent transcriptional activation.
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.
TGFA	Protransforming growth factor alpha	TGF alpha is a mitogenic polypeptide that is able to bind to the EGF receptor/EGFR and to act synergistically with TGF beta to promote anchorage-independent cell proliferation in soft agar.
ALDH1A2	Retinal dehydrogenase 2	Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively.
CCND1	G1/S-specific cyclin-D1	Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
CD274	Programmed cell death 1 ligand 1	Plays a critical role in induction and maintenance of immune tolerance to self.
CDKN1B	Cyclin-dependent kinase inhibitor 1B	Important regulator of cell cycle progression.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
DPYD	Dihydropyrimidine dehydrogenase [NADP(+)]	Involved in pyrimidine base degradation.
EGF	Pro-epidermal growth factor	EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture.
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
AREG	Amphiregulin	Ligand of the EGF receptor/EGFR.
SMAD4	SMAD family member 4	In muscle physiology, plays a central role in the balance between atrophy and hypertrophy.
MAPK1	Mitogen-activated protein kinase 1	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway.
NOTCH1	Neurogenic locus notch homolog protein 1	Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.
NRG1	Pro-neuregulin-1, membrane-bound isoform	Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors.
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.
PTPRT	Receptor-type tyrosine-protein phosphatase T	May be involved in both signal transduction and cellular adhesion in the CNS.
CCHCR1	Coiled-coil alpha-helical rod protein 1	May be a regulator of keratinocyte proliferation or differentiation.
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.

Protein-family classification

Druggable: 15 · Difficult: 4 · Unknown: 9 · Druggable fraction: 0.54

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
Kinase	6	5.9×	0.003
Phosphatase	2	6.0×	0.153
Antibody/Immunoglobulin	3	3.1×	0.162
Enzyme (other)	4	1.7×	0.353
Scaffold/PPI	2	1.2×	0.682
Transcription factor	2	0.6×	0.997
Other/Unknown	9	0.6×	0.997

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNFRSF10B	Other/Unknown	no		Death_dom, TNFR/NGFR_Cys_rich_reg, DEATH-like_dom_sf
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ING1	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
TGFA	Other/Unknown	no		EGF
ALDH1A2	Enzyme (other)	yes	1.2.1.36	Aldehyde_DH_dom, Ald_DH_CS_CYS, Ald_DH/histidinol_DH
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
CDKN1B	Other/Unknown	no		CDI_dom, CDI_dom_sf
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
DPYD	Enzyme (other)	yes	1.3.1.2	Dihydroorotate_DH_cat, Helical_ferredxn, Aldolase_TIM
EGF	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
AREG	Other/Unknown	no		EGF
SMAD4	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
MAPK1	Kinase	yes	2.7.11.24	Prot_kinase_dom, MAP_kinase_CS, Ser/Thr_kinase_AS
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
NRG1	Antibody/Immunoglobulin	yes		EGF, Neuregulin_C, Ig_sub2
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PTPRT	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, MAM_dom
POLR1HASP	Other/Unknown	no
CCHCR1	Other/Unknown	no		HCR
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set

Expression context

Cohort genes with no expression data: 0.

27 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)	28
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	6
ganglionic eminence	4
calcaneal tendon	4
stromal cell of endometrium	3
cartilage tissue	2
mucosa of urinary bladder	2
nipple	2
sperm	2
germinal epithelium of ovary	2
endometrium epithelium	2
right lung	2
Brodmann (1909) area 23	2
middle temporal gyrus	2
left testis	2
right testis	2
testis	2
blood	1
tendon of biceps brachii	1
gingiva	1
gingival epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNFRSF10B	289	ubiquitous	marker	cartilage tissue, mucosa of urinary bladder, blood
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
ING1	261	ubiquitous	marker	stromal cell of endometrium, ganglionic eminence, ventricular zone
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
TGFA	252	broad	yes	esophagus squamous epithelium, epithelium of esophagus, squamous epithelium
ALDH1A2	226	broad	marker	germinal epithelium of ovary, decidua, sperm
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung
CDKN1B	301	ubiquitous	marker	pigmented layer of retina, retina, ventricular zone
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
DPYD	274	ubiquitous	marker	germinal epithelium of ovary, monocyte, mononuclear cell
EGF	215	broad	marker	renal medulla, body of pancreas, hindlimb stylopod muscle
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
AREG	216	ubiquitous	marker	mucosa of urinary bladder, endometrium epithelium, right lung
SMAD4	288	ubiquitous	marker	ventricular zone, ganglionic eminence, calcaneal tendon
MAPK1	299	ubiquitous	marker	middle temporal gyrus, postcentral gyrus, Brodmann (1909) area 23
NOTCH1	272	ubiquitous	marker	ventricular zone, colonic epithelium, visceral pleura
NRG1	209	ubiquitous	marker	ventricular zone, ganglionic eminence, oocyte
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PTPRT	131	broad	marker	Brodmann (1909) area 10, middle temporal gyrus, Brodmann (1909) area 23
POLR1HASP	134	ubiquitous	marker	right testis, left testis, testis
CCHCR1	134	ubiquitous	marker	left testis, right testis, testis
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung

Protein interactions among cohort

Intra-cohort edges: 36.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
KRAS	14,509
PTEN	11,626
ERBB2	9,659
CDKN2A	9,311
CCND1	8,328
EGF	8,267
HRAS	8,064
MAPK1	8,003

Intra-cohort edges

A	B	Sources
AREG	EGF	string_interaction
AREG	EGFR	intact, string_interaction
AREG	ERBB2	string_interaction
AREG	TGFA	string_interaction
CCND1	CDKN1B	biogrid_interaction, intact, string_interaction
CCND1	CDKN2A	biogrid_interaction, string_interaction
CCND1	TP53	string_interaction
CDKN1B	TP53	string_interaction
CDKN2A	HRAS	string_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	TP53	string_interaction
EGF	EGFR	biogrid_interaction, intact, string_interaction
EGF	ERBB2	biogrid_interaction, string_interaction
EGF	TGFA	string_interaction
EGFR	ERBB2	intact, string_interaction
EGFR	HRAS	string_interaction
EGFR	NRG1	intact
EGFR	PIK3CA	string_interaction
EGFR	PTEN	string_interaction
EGFR	PTPRT	intact
EGFR	TGFA	intact, string_interaction
ERBB2	KRAS	string_interaction
ERBB2	PIK3CA	string_interaction
ERBB2	PTPRT	intact
ERBB2	TGFA	biogrid_interaction, string_interaction
FGFR1	FGFR2	intact
FGFR1	TNFRSF10B	biogrid_interaction
HRAS	TP53	string_interaction
KRAS	PIK3CA	string_interaction
KRAS	PTEN	string_interaction
KRAS	TP53	string_interaction
MAPK1	TP53	string_interaction
PIK3CA	PTEN	string_interaction
PTEN	SMAD4	string_interaction
PTEN	TP53	string_interaction
TNFRSF10B	TP53	string_interaction

Structural data

PDB: 25 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
EGFR	P00533	388
TP53	P04637	313
HRAS	P01112	246
MAPK1	P28482	160
PIK3CA	P42336	135
FGFR1	P11362	83
CD274	Q9NZQ7	76
ERBB2	P04626	63
FGFR2	P21802	63
NOTCH1	P46531	29
CDKN1B	P46527	19
TNFRSF10B	O14763	13
EGF	P01133	13
PTEN	P60484	12
SMAD4	Q13485	12
TGFA	P01135	11
CCND1	P24385	11
NRG1	Q02297	11
HLA-DQB1	P01920	10
ALDH1A2	O94788	7
CDKN2A	P42771	5
ING1	Q9UK53	1
AREG	P15514	1
PTPRT	O14522	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DPYD	Q12882	96.23
CCHCR1	Q8TD31	79.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 507. Enrichment computed across 28 evidence-associated genes (24 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 24 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RAF/MAP kinase cascade	12	30.5×	3e-13	EGFR, TGFA, EGF, ERBB2, FGFR1, FGFR2, HRAS, KRAS (+4 more)
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	10	40.3×	3e-12	EGFR, TGFA, EGF, ERBB2, FGFR1, FGFR2, AREG, MAPK1 (+2 more)
PIP3 activates AKT signaling	11	30.6×	3e-12	EGFR, TGFA, CDKN1B, EGF, ERBB2, FGFR1, FGFR2, AREG (+3 more)
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	7	128.1×	6e-12	EGFR, TGFA, CCND1, CDKN1B, EGF, AREG, MAPK1
Signaling by ERBB2 KD Mutants	7	123.4×	6e-12	EGFR, EGF, ERBB2, HRAS, KRAS, NRG1, PIK3CA
Constitutive Signaling by Aberrant PI3K in Cancer	9	47.6×	8e-12	EGFR, TGFA, EGF, ERBB2, FGFR1, FGFR2, AREG, NRG1 (+1 more)
GRB2 events in EGFR signaling	6	190.3×	2e-11	EGFR, TGFA, EGF, HRAS, KRAS, AREG
SHC1 events in EGFR signaling	6	178.4×	2e-11	EGFR, TGFA, EGF, HRAS, KRAS, AREG
Signaling by ERBB2 ECD mutants	6	167.9×	3e-11	EGFR, EGF, ERBB2, HRAS, KRAS, PIK3CA
Extra-nuclear estrogen signaling	8	56.8×	3e-11	EGFR, TGFA, CCND1, CDKN1B, EGF, AREG, MAPK1, PIK3CA
GRB2 events in ERBB2 signaling	6	158.6×	4e-11	EGFR, EGF, ERBB2, HRAS, KRAS, NRG1
SHC1 events in ERBB2 signaling	6	119.0×	2e-10	EGFR, EGF, ERBB2, HRAS, KRAS, NRG1
Signaling by ERBB2 TMD/JMD mutants	6	119.0×	2e-10	EGFR, EGF, ERBB2, HRAS, KRAS, NRG1
Constitutive Signaling by EGFRvIII	5	148.7×	4e-09	EGFR, EGF, HRAS, KRAS, PIK3CA
PI3K events in ERBB2 signaling	5	139.9×	5e-09	EGFR, EGF, ERBB2, NRG1, PIK3CA
GAB1 signalosome	5	132.2×	7e-09	EGFR, TGFA, EGF, AREG, PIK3CA
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	119.0×	1e-08	EGFR, EGF, HRAS, KRAS, PIK3CA
Developmental Lineage of Mammary Gland Myoepithelial Cells	5	113.3×	1e-08	EGFR, TGFA, EGF, ERBB2, AREG
Inhibition of Signaling by Overexpressed EGFR	4	211.5×	5e-08	EGFR, TGFA, EGF, AREG
EGFR interacts with phospholipase C-gamma	4	190.3×	8e-08	EGFR, TGFA, EGF, AREG
ERBB2 Activates PTK6 Signaling	4	135.9×	4e-07	EGFR, EGF, ERBB2, NRG1
ERBB2 Regulates Cell Motility	4	119.0×	6e-07	EGFR, EGF, ERBB2, NRG1
PLCG1 events in ERBB2 signaling	3	356.9×	7e-07	EGFR, EGF, ERBB2
Signaling by Nuclear Receptors	6	25.5×	2e-06	TGFA, ALDH1A2, CCND1, CDKN1B, AREG, MAPK1
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	4	76.1×	4e-06	TGFA, EGF, ERBB2, AREG
Estrogen-stimulated signaling through PRKCZ	3	203.9×	6e-06	HRAS, KRAS, MAPK1
Downregulation of ERBB2 signaling	4	63.4×	7e-06	EGFR, EGF, ERBB2, NRG1
Signaling by ERBB2	4	57.7×	1e-05	EGFR, EGF, ERBB2, NRG1
EGFR downregulation	4	57.7×	1e-05	EGFR, TGFA, EGF, AREG
FLT3 Signaling	4	57.7×	1e-05	CDKN1B, HRAS, KRAS, PIK3CA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 27 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ERBB2-EGFR signaling pathway	5	312.1×	2e-09	EGFR, TGFA, EGF, ERBB2, AREG
positive regulation of cell population proliferation	12	14.9×	2e-09	EGFR, PTEN, TGFA, ALDH1A2, CDKN1B, EGF, FGFR1, FGFR2 (+4 more)
epidermal growth factor receptor signaling pathway	7	64.2×	3e-09	EGFR, TGFA, EGF, ERBB2, AREG, MAPK1, PIK3CA
positive regulation of epithelial cell proliferation	6	54.3×	2e-07	EGFR, TGFA, ERBB2, FGFR2, HRAS, NOTCH1
negative regulation of cell population proliferation	9	14.0×	1e-06	TP53, ING1, PTEN, ALDH1A2, CDKN1B, CDKN2A, HRAS, SMAD4 (+1 more)
mammary gland alveolus development	4	146.9×	2e-06	TGFA, CCND1, EGF, AREG
positive regulation of MAPK cascade	7	20.9×	4e-06	EGFR, TGFA, EGF, ERBB2, FGFR1, FGFR2, HRAS
endocardial cell differentiation	3	312.1×	8e-06	SMAD4, NOTCH1, NRG1
positive regulation of cardiac muscle cell proliferation	4	92.5×	9e-06	FGFR1, FGFR2, NOTCH1, NRG1
cell surface receptor signaling pathway	7	16.6×	1e-05	TNFRSF10B, EGFR, TGFA, CD274, ERBB2, HRAS, MAPK1
ERBB2-ERBB3 signaling pathway	3	187.2×	3e-05	ERBB2, MAPK1, NRG1
mammary gland epithelial cell proliferation	3	170.2×	4e-05	CCND1, CDKN2A, MAPK1
negative regulation of cell growth	5	26.7×	7e-05	TP53, ING1, CDKN1B, CDKN2A, SMAD4
epithelial to mesenchymal transition	4	46.2×	1e-04	FGFR1, FGFR2, SMAD4, NOTCH1
Schwann cell development	3	117.0×	1e-04	ERBB2, HRAS, MAPK1
cellular senescence	4	43.8×	1e-04	TP53, CDKN1B, CDKN2A, HRAS
glial cell proliferation	3	98.5×	2e-04	TP53, KRAS, AREG
positive regulation of phosphorylation	3	93.6×	2e-04	EGFR, EGF, AREG
liver development	4	32.9×	3e-04	ALDH1A2, KRAS, NOTCH1, PIK3CA
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	2	416.1×	3e-04	FGFR1, FGFR2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	4	31.2×	3e-04	EGFR, PTEN, ERBB2, PIK3CA
Ras protein signal transduction	4	30.4×	3e-04	TP53, CDKN2A, HRAS, KRAS
cardiac muscle cell proliferation	3	64.6×	5e-04	FGFR1, KRAS, NOTCH1
ventricular zone neuroblast division	2	312.1×	5e-04	FGFR1, FGFR2
response to UV-A	2	312.1×	5e-04	EGFR, CCND1
positive regulation of ERK1 and ERK2 cascade	5	15.8×	5e-04	EGFR, FGFR2, HRAS, NOTCH1, NRG1
positive regulation of phospholipase activity	2	249.7×	7e-04	FGFR1, FGFR2
ERBB signaling pathway	2	249.7×	7e-04	MAPK1, NRG1
negative regulation of secretion	2	249.7×	7e-04	EGF, NRG1
MAPK cascade	4	22.7×	8e-04	FGFR1, HRAS, KRAS, MAPK1

Therapeutics

Drugs indicated for this disease

9 approved, 32 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Cemiplimab	Approved (phase 4)
Cetuximab	Approved (phase 4)
Cosibelimab	Approved (phase 4)
Docetaxel Anhydrous	Approved (phase 4)
Hydroxyurea	Approved (phase 4)
Nivolumab	Approved (phase 4)
Pembrolizumab	Approved (phase 4)
Retifanlimab	Approved (phase 4)
Temoporfin	Approved (phase 4)
Afatinib	Phase 3 (in late-stage trials)
Atezolizumab	Phase 3 (in late-stage trials)
Avelumab	Phase 3 (in late-stage trials)
Becotatug Vedotin	Phase 3 (in late-stage trials)
Benmelstobart	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Capecitabine	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Erlotinib	Phase 3 (in late-stage trials)
Ficlatuzumab	Phase 3 (in late-stage trials)
Finotonlimab	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Gefitinib	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Hafnium Oxide	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Lenvatinib	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Monalizumab	Phase 3 (in late-stage trials)
Nedaplatin	Phase 3 (in late-stage trials)
Nimorazole	Phase 3 (in late-stage trials)
Nimotuzumab	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Palbociclib	Phase 3 (in late-stage trials)
Panitumumab	Phase 3 (in late-stage trials)
Penpulimab	Phase 3 (in late-stage trials)
Tirapazamine	Phase 3 (in late-stage trials)
Tremelimumab	Phase 3 (in late-stage trials)
Volrustomig	Phase 3 (in late-stage trials)
Xevinapant	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abemaciclib, Acalabrutinib, Adebrelimab, Albumin Human, Alpelisib, Axitinib, Bevacizumab, Bintrafusp Alfa, Bleomycin, Buparlisib, Buprenorphine, Cabazitaxel, Cadonilimab, Catequentinib, Ceralasertib, Dacomitinib Anhydrous, Dalantercept, Dalpiciclib, Dasatinib Anhydrous, Demplatin Pegraglumer, Dexamethasone, Duvelisib, Epacadostat, Everolimus, Filgrastim, Gimeracil, Ibrutinib, Indomethacin, Infigratinib, Isosorbide, Izalontamab, Lapatinib, Lifileucel, Lobaplatin, Magrolimab, Metformin, Mitomycin, Niraparib, Nogapendekin Alfa, Olaparib, Omeprazole, Oteracil, Oxygen, Pazopanib, Pegfilgrastim, Pemetrexed, Pirfenidone, Ramucirumab, Relatlimab, Retlirafusp Alfa, Rigosertib, Rilvegostomig, Rivoceranib, Ruxolitinib, Sargramostim, Serplulimab, Sintilimab, Sodium Dichloroacetate, Sulindac, Sunitinib, Surzebiclimab, Tadalafil, Tegafur, Temsirolimus, Tipifarnib, Tiragolumab, Tislelizumab, Tivantinib, Toripalimab, Tramadol, Valproic Acid, Vandetanib, Zanzalintinib, Zimberelimab, Zinc Ion.

Drug target analysis

Approved (phase 4): 11 · Phase ≥3: 12 · Phased (≥1): 13 · Undrugged: 15

Druggability breadth: 22 of 28 evidence-associated genes (79%) 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
TP53	NITROFURANTOIN
EGFR	LEVODOPA
CCND1	PALBOCICLIB
CD274	MOCLOBEMIDE
ERBB2	CLOTRIMAZOLE
FGFR1	PONATINIB
FGFR2	PONATINIB
HRAS	LONAFARNIB
KRAS	VEMURAFENIB
MAPK1	PHENYLBUTAZONE
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAPK1	324	4
TP53	196	4
EGFR	175	4
FGFR1	93	4
ERBB2	83	4
PIK3CA	67	4
FGFR2	59	4
CCND1	35	4
KRAS	11	4
CD274	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	MAPK1, TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	EGFR, ERBB2, MAPK1, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	MAPK1, TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	MAPK1, TP53
SULCONAZOLE NITRATE	4	MAPK1, TP53
PYRITHIONE ZINC	4	MAPK1, TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	MAPK1, TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	MAPK1, TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	MAPK1, TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	MAPK1, TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	MAPK1, TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
MAPK1	1,369	Binding:1348, Functional:16, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
FGFR2	966	Binding:940, Functional:22, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
CCND1	576	Binding:574, Functional:1, ADMET:1
CD274	525	Binding:520, Functional:5
HRAS	48	Binding:45, Functional:3
ALDH1A2	32	Binding:32
NOTCH1	23	Binding:19, ADMET:4
TNFRSF10B	9	Binding:9
PTEN	8	Binding:8
SMAD4	6	Binding:6
CDKN1B	5	Binding:5
EGF	5	Binding:5
TGFA	3	Binding:3
DPYD	3	Functional:2, Binding:1
CDKN2A	2	Binding:2
AREG	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EGFR	2.7.10.1	receptor protein-tyrosine kinase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
ALDH1A2	1.2.1.36	retinal dehydrogenase
DPYD	1.3.1.2	dihydropyrimidine dehydrogenase (NADP+)
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
HRAS	3.6.5.2	small monomeric GTPase
KRAS	3.6.5.2	small monomeric GTPase
MAPK1	2.7.11.24	mitogen-activated protein kinase
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
PTPRT	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
TP53	869
EGFR	6,531
CCND1	576
CD274	525
ERBB2	1,221
FGFR1	1,465
FGFR2	966
KRAS	861
MAPK1	1,369
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 28; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
DPYD	1

Drug repurposing candidates

30 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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	MAPK1, TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	EGFR, ERBB2, MAPK1, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	MAPK1, TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	MAPK1, TP53
SULCONAZOLE NITRATE	4	MAPK1, TP53
PYRITHIONE ZINC	4	MAPK1, TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	MAPK1, TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	MAPK1, TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	MAPK1, TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	MAPK1, TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	MAPK1, TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	11	TP53, EGFR, CCND1, CD274, ERBB2, FGFR1, FGFR2, HRAS, KRAS, MAPK1 (+1 more)
B	Phased (≥1) drug, not yet approved	2	DPYD, NOTCH1
C	Druggable family + PDB, no drug	5	PTEN, ALDH1A2, NRG1, PTPRT, HLA-DQB1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	10	TNFRSF10B, ING1, TGFA, CDKN1B, CDKN2A, EGF, AREG, SMAD4, POLR1HASP, CCHCR1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PTEN	8	TP53
TGFA	3	EGFR, ERBB2
EGF	5	EGFR, ERBB2
AREG	1	EGFR
NRG1	0	EGFR
TNFRSF10B	9	—
ING1	0	—
ALDH1A2	32	—
CDKN1B	5	—
CDKN2A	2	—
SMAD4	6	—
PTPRT	0	—
POLR1HASP	0	—
CCHCR1	0	—
HLA-DQB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,051.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	361
PHASE1	255
Not specified	191
PHASE1/PHASE2	135
PHASE3	62
EARLY_PHASE1	31
PHASE2/PHASE3	9
PHASE4	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06162377	PHASE4	RECRUITING	Methylnatrexone In Resectable Head and Neck Squamous Cell Carcinoma (MINK). A Window of Opportunity Pilot Study.
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT01344356	PHASE4	COMPLETED	Stereotactic Body Radiotherapy for Head and Neck Tumors
NCT03196843	PHASE4	UNKNOWN	Radiotherapy Combine With Raltitrexed Versus Radiotherapy Alone in Older Patients With HNSCC.
NCT03998696	PHASE4	COMPLETED	An Experimental Study to Compare Treatment Response and Toxicities of Concurrent Chemoradiation With Weekly Cisplatin and Three Weekly Cisplatin in Locally Advanced Head and Neck Cancer.
NCT04489888	PHASE4	COMPLETED	A Study of Pembrolizumab (MK-3475) Plus Carboplatin and Paclitaxel as First-line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (MK-3475-B10/KEYNOTE B10)
NCT04766827	PHASE4	UNKNOWN	Albumin-bound Paclitaxel Combined With Cisplatin Versus Docetaxel Combined With Cisplatin Induced Chemotherapy in Advanced Head and Neck Squamous Tummor
NCT02998385	PHASE3	ACTIVE_NOT_RECRUITING	Chemo-radiotherapy Versus Radiotherapy in the Treatment of Salivary Glands and Nasal Tumors (IMRT or Protontherapy)
NCT02999087	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Trial of Avelumab-cetuximab-radiotherapy Versus SOCs in LA SCCHN (REACH)
NCT03340896	PHASE3	ACTIVE_NOT_RECRUITING	Trial of Laryngeal Preservation Comparing Induced CT Followed by RT vs CT Concomitant to RT
NCT03519048	PHASE3	ACTIVE_NOT_RECRUITING	Multicentric Comparative Study Between a Conventional and an Intensive Follow up Strategy After Treatment of a Head and Neck Squamous Cell Carcinoma
NCT03576417	PHASE3	ACTIVE_NOT_RECRUITING	A Trial Evaluating the Addition of Nivolumab to Cisplatin-RT for Treatment of Cancers of the Head and Neck
NCT04590963	PHASE3	ACTIVE_NOT_RECRUITING	Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer
NCT04747054	PHASE3	RECRUITING	Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers
NCT05044117	PHASE3	RECRUITING	Single-agent Capecitabine as Metronomic Chemotherapy in LAHNSCC (CMHN)
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
NCT05582265	PHASE3	RECRUITING	Tislelizumab Combined With Chemotherapy Followed by Surgery Versus Up-front Surgery in Resectable Head and Neck Squamous Cell Carcinoma (REDUCTION-I)
NCT05721755	PHASE3	ACTIVE_NOT_RECRUITING	Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT05980715	PHASE3	RECRUITING	PD-1 Inhibitor Therapy Versus Radiotherapy in pCR Patients With Locally Advanced HNSCC After Neoadjuvant Immunochemotherapy
NCT06064877	PHASE3	RECRUITING	A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma
NCT06082167	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Study of Zanzalintinib (XL092) + Pembrolizumab vs Pembrolizumab in Subjects With PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
NCT06102395	PHASE3	RECRUITING	Evaluating the Efficacy and Safety of Pembrolizumab Plus Standard Chemotherapy in the Neoadjuvant Treatment of Local Advanced (LA) HNSCC
NCT06129864	PHASE3	RECRUITING	A Global Study of Volrustomig (MEDI5752) for Participants With Unresected Locally Advanced Head and Neck Squamous Cell Carcinoma Following Definitive Concurrent Chemoradiotherapy
NCT06248996	PHASE3	RECRUITING	a Multicentre Phase III Study of Risk-based Treatment Intensification With Hyperfractionated Radiotherapy in Head and Neck Cancer Patients
NCT06295731	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	INBRX-106 in Combination With Pembrolizumab in First-line PD-L1 CPS≥20 HNSCC
NCT06492460	PHASE3	RECRUITING	2 Courses of Concurrent Cisplatin Chemoradiotherapy After Surgery for High-risk Head and Neck Squamous Cell Carcinoma
NCT06496178	PHASE3	RECRUITING	A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator’s Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients (LiGeR-HN2)
NCT06525220	PHASE3	RECRUITING	A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Head and Neck Cancer (LiGeR - HN1)
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
NCT06601335	PHASE3	RECRUITING	A Phase 3 Study of AK112 Plus AK117 Versus Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
NCT06647563	PHASE3	NOT_YET_RECRUITING	Neoadjuvant Toripalimab + Chemotherapy ± Cetuximab in Locally Advanced Head and Neck Squamous Cell Carcinoma (Neo-ICT)
NCT06699212	PHASE3	RECRUITING	A Study of ASP-1929 Photoimmunotherapy in Combination With Pembrolizumab in First-line Treatment of Locoregional Recurrent Squamous Cell Carcinoma of the Head and Neck With No Distant Metastases
NCT06719479	PHASE2/PHASE3	NOT_YET_RECRUITING	A Clinical Trial to Evaluate Effect of IAE0972 Combined with Chemotherapy for R/M HNSCC or NPC(Note: It is Currently Phase II.).
NCT06788990	PHASE2/PHASE3	RECRUITING	FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab in First-Line PD-L1-pos, R or M HNSCC
NCT06992427	PHASE3	RECRUITING	High-dose Prophylactic Gabapentin (HOPE) vs. Placebo to Prevent Opioid Use for Oral Mucositis Pain During Concurrent Chemoradiation for Head and Neck Cancer
NCT07026474	PHASE3	RECRUITING	Re-Radiochemotherapy and Pembrolizumab vs. Immuno(Chemo)Therapy for Locoregionally Recurrent PD-L1 Positive (CPS≥1) HNSCC
NCT07276399	PHASE3	RECRUITING	A Study of Amivantamab in Addition to Standard of Care Agents (SOC) Compared With SOC Alone in Participants With Recurrent/Metastatic Head and Neck Cancer
NCT07320690	PHASE3	NOT_YET_RECRUITING	De-Escalation Surgery After Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma
NCT07432087	PHASE3	NOT_YET_RECRUITING	Camrelizumab Combined With EGFR Monoclonal Antibody or Chemotherapy for Perioperative Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma
NCT07435324	PHASE3	ACTIVE_NOT_RECRUITING	A Comparative Study of Efficacy and Safety of RPH-002 and Erbitux® in Unresectable Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CISPLATIN	4	117
CETUXIMAB	4	15
TREMELIMUMAB	4	7
RETIFANLIMAB	4	5
AVELUMAB	4	4
AFATINIB	4	3
NIVOLUMAB	4	3
DURVALUMAB	4	2
LENVATINIB	4	2
METHYLNALTREXONE	4	2
PACLITAXEL	4	2
TECHNETIUM TC 99M TILMANOCEPT	4	2
TILMANOCEPT	4	2
ATEZOLIZUMAB	4	1
CARBOPLATIN	4	1
DAPSONE	4	1
ERLOTINIB	4	1
GEFITINIB	4	1
PEMBROLIZUMAB	4	1
RALTITREXED	4	1
BECOTATUG VEDOTIN	3	5
XEVINAPANT	3	5
BENMELSTOBART	3	3
FICLATUZUMAB	3	3
FINOTONLIMAB	3	2
NIMORAZOLE	3	2
ZANZALINTINIB	3	2
MONALIZUMAB	3	1
TIRAPAZAMINE	3	1
TEBOTELIMAB	2	3

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 43 predictive associations from 44 curated evidence items; also 18 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
CDKN1B EXPRESSION	Cisplatin + Fluorouracil	Sensitivity/Response	CIViC B	EID889
CDKN2A p16 Expression	Panitumumab	Sensitivity/Response	CIViC B	EID753
EGFR Amplification	Fluorouracil + Platinum Compound + Cetuximab	Sensitivity/Response	CIViC B	EID691
EGFR Overexpression	Cetuximab	Sensitivity/Response	CIViC B	EID692
EGFR Overexpression	Cetuximab + Docetaxel	Sensitivity/Response	CIViC B	EID849
HRAS Mutation	Tipifarnib	Sensitivity/Response	CIViC B	EID9633
PIK3CA Amplification	Ibuprofen + Aspirin + Sulindac	Sensitivity/Response	CIViC B	EID7186
PIK3CA Mutation	Aspirin + Sulindac + Celecoxib	Sensitivity/Response	CIViC B	EID7185
TMB High	Durvalumab	Sensitivity/Response	CIViC B	EID12850
AREG Expression	Docetaxel + Cetuximab	Resistance	CIViC B	EID846
CD274 Expression	Radiation Therapy	Resistance	CIViC B	EID3000
CDKN2A p16 Expression	Afatinib	Resistance	CIViC B	EID1155
CDKN2A p16 Expression	Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor	Resistance	CIViC B	EID694
CDKN2A p16 Expression	Panitumumab	Resistance	CIViC B	EID696
CDKN2A p16 Expression	Cetuximab	Resistance	CIViC B	EID697
EGFR VIII	Cetuximab + Docetaxel	Resistance	CIViC B	EID848
KRAS RS61764370	Cisplatin	Resistance	CIViC B	EID872
NRAS G13V	Cetuximab	Resistance	CIViC B	EID3035
MAPK1 E322K	Erlotinib	Sensitivity/Response	CIViC C	EID791 +1
DPYD EXON 11-19 DELETION	Leucovorin + Fluorouracil	Sensitivity/Response	CIViC C	EID7787
ERBB2 Overexpression	Lapatinib	Sensitivity/Response	CIViC C	EID1992
FGFR2 P253R	Pazopanib	Sensitivity/Response	CIViC C	EID7833
MAPK1 E278E	Erlotinib	Sensitivity/Response	CIViC C	EID4607
PIK3CA E542K	Apitolisib	Sensitivity/Response	CIViC C	EID1549
ALDH1A2 Underexpression	Tretinoin	Sensitivity/Response	CIViC D	EID1115
AURKB Overexpression	Alisertib + Barasertib + Copanlisib	Sensitivity/Response	CIViC D	EID10836
EGFR Amplification	Afatinib + Erlotinib + Cetuximab	Sensitivity/Response	CIViC D	EID9674
EGFR P546S	Cetuximab	Sensitivity/Response	CIViC D	EID4672
ERBB2 S1050L	Erlotinib + Cetuximab + Afatinib	Sensitivity/Response	CIViC D	EID9680
ERBB3 R1202W	Erlotinib + Cetuximab	Sensitivity/Response	CIViC D	EID9681

+13 more predictive associations (showing top 30 by evidence level).