Esophageal cancer

Summary

Esophageal cancer (MONDO:0007576) is a cancer (an umbrella term covering 7 Mondo subtypes) with 10 cohort genes (52 GWAS associations across 17 studies; 8 CIViC-evidence somatic drivers; 87 ClinVar predisposition records) and 1,301 clinical trials. Molecularly, GNAS c.393T>C is associated with resistance to Cisplatin + Fluorouracil in Esophageal Cancer (CIViC Level B); 7 further subtype–drug associations are mapped below. Top therapeutic interventions include irinotecan, bevacizumab, and epirubicin.

At a glance

• Classification: Cancer
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 10
• GWAS associations: 52
• ClinVar variants: 87
• Clinical trials: 1,301
• Precision-medicine evidence (CIViC): 8 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	esophageal cancer
Mondo ID	MONDO:0007576
OMIM	133239
DOID	DOID:5041
ICD-10-CM	C15
ICD-11	669033105
NCIT	C7478
SNOMED CT	363402007
UMLS	C0546837
MedGen	107792
GARD	0027778
Anatomy (UBERON)	UBERON:0001043
Is cancer (heuristic)	yes

Also known as: Ca lower third esophagus · Ca lower third oesophagus · Ca middle third esophagus · Ca middle third oesophagus · cancer of esophagus · cancer of oesophagus · esophageal cancer · esophageal cancer, somatic · esophageal carcinoma, somatic · esophageal squamous cell carcinoma, somatic · esophagus cancer · malignant esophageal neoplasm · malignant esophageal tumor · malignant esophageal tumour · malignant esophagus neoplasm · malignant esophagus tumor · malignant neoplasm of distal third of esophagus · malignant neoplasm of distal third of oesophagus · malignant neoplasm of esophagus · malignant neoplasm of lower third of esophagus (+25 more)

Data availability: 87 ClinVar variants · 52 GWAS associations (17 studies) · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 7 Mondo subtypes.

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

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

Subtypes (7): esophagus lymphoma, esophageal melanoma, esophagus sarcoma, carcinoma of esophagus, malignant neoplasm of abdominal esophagus, malignant neoplasm of thoracic esophagus, malignant neoplasm of cervical esophagus

Genetics & variants

GWAS landscape

52 GWAS associations across 17 studies. Top hits map to 35 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1229984	3e-44	ADH1B	C	2.14
rs12682374	9e-29	PCAT1, CASC8, POU5F1B	?	0.93
rs1219651	1e-25	FGFR2	?	1.09
rs2981584	1e-21	FGFR2	?	0.94
rs10908278	3e-21	HNF1B	?	1.06
rs112149573	2e-17	TOX3	?	1.08
rs79105258	2e-17	CUX2	?	0.17
rs78540526	1e-15	LINC01488 - PNCRNA-D	?	1.13
rs35409710	2e-15	HLA-DQB1	?	1.09
rs7463708	2e-15	PCAT1, PRNCR1, CASC19	?	1.08
rs11651755	1e-14	HNF1B	?	1.06
rs1485995	8e-14	LINC01488	?	0.95
rs9273736	2e-13	HLA-DQB1	?	1.12
rs2976384	3e-13	PSCA, JRK	?	1.07
rs2585181	3e-12	PSCA - LY6K	?	1.05
rs4007642	6e-11	CDKN2B-AS1	?	0.96
rs10786774	1e-10	STN1	?	0.92
rs2990223	1e-10	GBA1LP, GBA1LP	?	1.09
rs4442975	2e-10	TESHL	?	0.96
rs4630240	2e-10	RPL23AP61	?	0.96
rs1859963	8e-10	CASC17	?	0.96
rs11813268	8e-10	STN1 - SLK	?	1.05
rs10891246	2e-09	POU2AF3, COLCA1	?	0.96
rs1827336845	2e-09	CHCHD4P2 - RPL36P14	?	1.05
rs11065836	3e-09	CUX2	?	1.26
rs6913578	3e-09	CCDC170 - ESR1	?	1.04
rs2525548	3e-09	Y_RNA - AZGP1	?	0.96
rs205780	3e-09	LINC-PINT	?	1.05
rs2237896	5e-09	KCNQ1	?	1.05
rs778188682	7e-09	C5orf67 - MAP3K1	?	1.07

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90651054	Sato G	2023	43,098	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90308764	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651069	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90477174	Verma A	2024	2,058	448,337	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651045	Sato G	2023	1,387	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90308755	Sato G	2023	1,159	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651060	Sato G	2023	1,159	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90503277	Wilcox N	2025	1,022	418,285	The contribution of coding variants to the heritability of multiple cancer types using UK Biobank whole-exome sequencing data.
GCST90079575	Backman JD	2021	992	386,907	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083561	Backman JD	2021	992	386,907	Exome sequencing and analysis of 454,787 UK Biobank participants.

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	1
Tier 4: intronic/intergenic	42

MAF distribution

Bucket	Variants
common (>=0.05)	42
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	31
intergenic_variant	8
non_coding_transcript_exon_variant	3
missense_variant	1
regulatory_region_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1229984	4	99318162	T>A,C,G	0.05	missense_variant	ADH1B	3e-44	Tier 1: coding
rs12682374	8	127398703	C>A,G,T	0.05	intron_variant	PCAT1, CASC8, POU5F1B	9e-29	Tier 4: intronic/intergenic
rs1219651	10	121584987	G>A,C,T	0.05	intron_variant	FGFR2	1e-25	Tier 4: intronic/intergenic
rs2981584	10	121590702	A>C,G,T	0.05	intron_variant	FGFR2	1e-21	Tier 4: intronic/intergenic
rs10908278	17	37739961	A>C,G,T	0.05	intron_variant	HNF1B	3e-21	Tier 4: intronic/intergenic
rs112149573	16	52547333	G>C,T	0.05	intron_variant	TOX3	2e-17	Tier 4: intronic/intergenic
rs79105258	12	111280427	C>A,T	0.05	intron_variant	CUX2	2e-17	Tier 4: intronic/intergenic
rs78540526	11	69516650	C>T	0.05	regulatory_region_variant	LINC01488 - PNCRNA-D	1e-15	Tier 3: regulatory
rs35409710	6	32661126	G>A	0.05	intron_variant	HLA-DQB1	2e-15	Tier 4: intronic/intergenic
rs7463708	8	127091810	G>A,C,T	0.05	non_coding_transcript_exon_variant	PCAT1, PRNCR1, CASC19	2e-15	Tier 4: intronic/intergenic
rs11651755	17	37739849	T>C	0.05	intron_variant	HNF1B	1e-14	Tier 4: intronic/intergenic
rs1485995	11	69492939	G>A,C	0.05	non_coding_transcript_exon_variant	LINC01488	8e-14	Tier 4: intronic/intergenic
rs9273736	6	32661595	G>A,C	0.05	intron_variant	HLA-DQB1	2e-13	Tier 4: intronic/intergenic
rs2976384	8	142671576	T>A,C	0.05	intergenic_variant	PSCA, JRK	3e-13	Tier 4: intronic/intergenic
rs2585181	8	142690296	C>A	0.05	intergenic_variant	PSCA - LY6K	3e-12	Tier 4: intronic/intergenic
rs4007642	9	22093300	A>C,T	0.05	intron_variant	CDKN2B-AS1	6e-11	Tier 4: intronic/intergenic
rs10786774	10	103884565	G>A,C,T	0.05	intron_variant	STN1	1e-10	Tier 4: intronic/intergenic
rs2990223	1	155215184	G>A,T	0.05	intron_variant	GBA1LP, GBA1LP	1e-10	Tier 4: intronic/intergenic
rs4442975	2	217056046	G>A,C,T	0.05	intron_variant	TESHL	2e-10	Tier 4: intronic/intergenic
rs4630240	10	46063294	C>A,T	0.05	non_coding_transcript_exon_variant	RPL23AP61	2e-10	Tier 4: intronic/intergenic
rs1859963	17	71116966	T>A,C	0.05	intron_variant	CASC17	8e-10	Tier 4: intronic/intergenic
rs11813268	10	103922538	C>T	0.05	intron_variant	STN1 - SLK	8e-10	Tier 4: intronic/intergenic
rs10891246	11	111299815	A>G,T	0.05	intron_variant	POU2AF3, COLCA1	2e-09	Tier 4: intronic/intergenic
rs1827336845	9	108131440	GGTATT>G		intergenic_variant	CHCHD4P2 - RPL36P14	2e-09	Tier 4: intronic/intergenic
rs11065836	12	111233272	G>A,C	0.05	intron_variant	CUX2	3e-09	Tier 4: intronic/intergenic
rs6913578	6	151628671	A>C,T	0.05	intergenic_variant	CCDC170 - ESR1	3e-09	Tier 4: intronic/intergenic
rs2525548	7	99955544	C>A,G,T	0.05	intergenic_variant	Y_RNA - AZGP1	3e-09	Tier 4: intronic/intergenic
rs205780	7	130966100	G>A	0.05	intron_variant	LINC-PINT	3e-09	Tier 4: intronic/intergenic
rs2237896	11	2837210	G>A,T	0.05	intron_variant	KCNQ1	5e-09	Tier 4: intronic/intergenic
rs778188682	5	56757919			intergenic_variant	C5orf67 - MAP3K1	7e-09	Tier 4: intronic/intergenic

ClinVar germline variants

87 retrieved; paginated sample, class counts are floors:

32 uncertain significance, 19 conflicting classifications of pathogenicity, 11 benign/likely benign, 6 pathogenic/likely pathogenic, 6 pathogenic, 5 uncertain significance/uncertain risk allele, 4 likely benign, 3 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028591	NM_003242.6(TGFBR2):c.1134G>C (p.Arg378Ser)	TGFBR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12503	NM_003242.6(TGFBR2):c.1576G>C (p.Glu526Gln)	TGFBR2	Pathogenic	criteria provided, single submitter
12519	NM_003242.6(TGFBR2):c.1483C>T (p.Arg495Ter)	TGFBR2	Pathogenic	criteria provided, multiple submitters, no conflicts
1686258	NM_003242.6(TGFBR2):c.1447del (p.Cys483fs)	TGFBR2	Pathogenic	criteria provided, single submitter
449834	NM_003242.6(TGFBR2):c.913C>T (p.Leu305Phe)	TGFBR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
811253	NM_003242.6(TGFBR2):c.1561T>C (p.Trp521Arg)	TGFBR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12374	NM_000546.6(TP53):c.524G>A (p.Arg175His)	TP53	Pathogenic	reviewed by expert panel
634674	NM_000546.6(TP53):c.298del (p.Gln100fs)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
984966	NM_000546.6(TP53):c.628_639del (p.Asn210_Arg213del)	TP53	Pathogenic	criteria provided, single submitter
1686306	NM_016373.4(WWOX):c.1056G>C (p.Met352Ile)	WWOX	Pathogenic	criteria provided, single submitter
241105	NM_016373.4(WWOX):c.790C>T (p.Arg264Ter)	WWOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
813767	NM_016373.4(WWOX):c.689A>C (p.Gln230Pro)	WWOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
804478	NM_016373.4(WWOX):c.108-2A>T	WWOX	Likely pathogenic	criteria provided, single submitter
344652	NM_003242.6(TGFBR2):c.-193G>A	LOC129936399	Uncertain significance/Uncertain risk allele	criteria provided, multiple submitters, no conflicts
1001410	NM_003242.6(TGFBR2):c.-337T>A	TGFBR2	Uncertain significance/Uncertain risk allele	criteria provided, multiple submitters, no conflicts
858705	NM_003242.6(TGFBR2):c.76C>T (p.Pro26Ser)	TGFBR2	Uncertain significance/Uncertain risk allele	criteria provided, multiple submitters, no conflicts
920747	NM_003242.6(TGFBR2):c.1A>G (p.Met1Val)	TGFBR2	Uncertain significance/Uncertain risk allele	criteria provided, multiple submitters, no conflicts
927079	NM_003242.6(TGFBR2):c.340G>C (p.Glu114Gln)	TGFBR2	Uncertain significance/Uncertain risk allele	criteria provided, multiple submitters, no conflicts
1202728	NM_003242.6(TGFBR2):c.1490G>A (p.Arg497Gln)	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1363915	NM_003242.6(TGFBR2):c.797A>G (p.Asn266Ser)	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213913	NM_003242.6(TGFBR2):c.94+16293C>A	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213915	NM_003242.6(TGFBR2):c.412T>G (p.Cys138Gly)	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213942	NM_003242.6(TGFBR2):c.760C>T (p.Arg254Cys)	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
239526	NM_003242.6(TGFBR2):c.116C>A (p.Thr39Asn)	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
344646	NM_003242.6(TGFBR2):c.-371A>C	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
344648	NM_003242.6(TGFBR2):c.-307C>T	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
374980	NM_003242.6(TGFBR2):c.1015C>T (p.Arg339Trp)	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
408434	NM_003242.6(TGFBR2):c.95-3C>A	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
408436	NM_003242.6(TGFBR2):c.1126G>A (p.Val376Met)	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
408442	NM_003242.6(TGFBR2):c.215G>A (p.Ser72Asn)	TGFBR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 64 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
DCC	LoF	COADREAD,ESCA,HCC,PAAD,PRAD	CIViC #1396
RNF6	LoF	COADREAD
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
GNAS	Act	BRCA,COADREAD,ESCA,HCC,LUAD,MBL,PAAD,PANCREAS	CIViC #2319
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
TGFBR2	LoF	CCRCC,CEAD,CESC,COADREAD,ESCA,HNSC,PAAD,PANCREAS,STAD
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
MAF	Act	PCM

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
DCC	No Known Disease Relationship	Unknown	esophageal cancer	12
RNF6	No Known Disease Relationship	Unknown	esophageal cancer

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCC	Orphanet:238722	Familial congenital mirror movements
DCC	Orphanet:2744	Horizontal gaze palsy with progressive scoliosis
DCC	Orphanet:478	Kallmann syndrome
RNF6	Orphanet:99977	Squamous cell carcinoma of the esophagus
ERBB2	Orphanet:213726	Serous carcinoma of the corpus uteri
ERBB2	Orphanet:2800	Extramammary Paget disease
ERBB2	Orphanet:388	Hirschsprung disease
ERBB2	Orphanet:99976	Adenocarcinoma of the oesophagus and oesophagogastric junction
GNAS	Orphanet:189427	Cushing syndrome due to bilateral macronodular adrenocortical disease
GNAS	Orphanet:2762	Progressive osseous heteroplasia
GNAS	Orphanet:562	McCune-Albright syndrome
GNAS	Orphanet:57782	Mazabraud syndrome
GNAS	Orphanet:79443	Pseudohypoparathyroidism type 1A
GNAS	Orphanet:79444	Pseudohypoparathyroidism type 1C
GNAS	Orphanet:79445	Pseudopseudohypoparathyroidism
GNAS	Orphanet:93276	Polyostotic fibrous dysplasia
GNAS	Orphanet:93277	Monostotic fibrous dysplasia
GNAS	Orphanet:94089	Pseudohypoparathyroidism type 1B
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
TGFBR2	Orphanet:144	Lynch syndrome
TGFBR2	Orphanet:284973	Marfan syndrome type 2
TGFBR2	Orphanet:60030	Loeys-Dietz syndrome
TGFBR2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
TGFBR2	Orphanet:99977	Squamous cell carcinoma of the esophagus
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

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DCC	HGNC:2701	ENSG00000187323	P43146	Netrin receptor DCC	gencc,clinvar
RNF6	HGNC:10069	ENSG00000127870	Q9Y252	E3 ubiquitin-protein ligase RNF6	gencc
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
GNAS	HGNC:4392	ENSG00000087460	O95467	Neuroendocrine secretory protein 55	civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
TGFBR2	HGNC:11773	ENSG00000163513	P37173	TGF-beta receptor type-2	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
WWOX	HGNC:12799	ENSG00000186153	Q9NZC7	WW domain-containing oxidoreductase	clinvar
DLEC1	HGNC:2899	ENSG00000008226	Q9Y238	Deleted in lung and esophageal cancer protein 1	clinvar
MAF	HGNC:6776	ENSG00000178573	O75444	Transcription factor Maf	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCC	Netrin receptor DCC	Receptor for netrin required for axon guidance.
RNF6	E3 ubiquitin-protein ligase RNF6	E3 ubiquitin-protein ligase mediating ‘Lys-48’-linked polyubiquitination of LIMK1 and its subsequent targeting to the proteasome for degradation.
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.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
TGFBR2	TGF-beta receptor type-2	Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
WWOX	WW domain-containing oxidoreductase	Putative oxidoreductase.
DLEC1	Deleted in lung and esophageal cancer protein 1	Essential for spermatogenesis and male fertility.
MAF	Transcription factor Maf	Acts as a transcriptional activator or repressor.

Protein-family classification

Druggable: 4 · Difficult: 4 · Unknown: 2 · Druggable fraction: 0.4

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	2	5.8×	0.121
Kinase	2	5.5×	0.121
Transcription factor	3	2.5×	0.185
Scaffold/PPI	1	1.7×	0.561
Other/Unknown	2	0.4×	0.996

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DCC	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
RNF6	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, RING_finger_E3_ligase
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
GNAS	Other/Unknown	no		NESP55, Gprotein_alpha_S, Gprotein_alpha_su
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
TGFBR2	Kinase	yes	2.7.10.2	TGFB_receptor, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
WWOX	Scaffold/PPI	no		WW_dom, SDR_fam, WW_dom_sf
DLEC1	Antibody/Immunoglobulin	yes		Ig-like_fold, DLEC1, Ig_DLEC1_1
MAF	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf

Expression context

Cohort genes with no expression data: 0.

10 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	2
right uterine tube	2
ventricular zone	2
cortical plate	1
left testis	1
right testis	1
choroid plexus epithelium	1
epithelium of nasopharynx	1
lower esophagus mucosa	1
sural nerve	1
Brodmann (1909) area 46	1
postcentral gyrus	1
type B pancreatic cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1
parietal pleura	1
pericardium	1
tibia	1
ganglionic eminence	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCC	154	broad	marker	cortical plate, right testis, left testis
RNF6	294	ubiquitous	marker	bronchial epithelial cell, epithelium of nasopharynx, choroid plexus epithelium
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
GNAS	312	ubiquitous	marker	type B pancreatic cell, postcentral gyrus, Brodmann (1909) area 46
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
TGFBR2	289	ubiquitous	marker	pericardium, tibia, parietal pleura
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
WWOX	286	ubiquitous	marker	parotid gland, cervix squamous epithelium, cranial nerve II
DLEC1	188	broad	marker	right uterine tube, epithelium of bronchus, bronchial epithelial cell
MAF	290	ubiquitous	marker	jejunal mucosa, germinal epithelium of ovary, gingiva

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
ERBB2	9,659
WWOX	5,892
TGFBR2	5,777
BRCA2	4,839
MAF	4,111
DCC	1,333
DLEC1	1,229
RNF6	1,187
GNAS	410

Intra-cohort edges

A	B	Sources
BRCA2	TP53	string_interaction
DLEC1	RNF6	string_interaction
DLEC1	WWOX	string_interaction
ERBB2	TGFBR2	biogrid_interaction
RNF6	WWOX	string_interaction
TP53	WWOX	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAS	O95467	490
TP53	P04637	313
ERBB2	P04626	63
TGFBR2	P37173	22
BRCA2	P51587	14
DCC	P43146	9
WWOX	Q9NZC7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DLEC1	Q9Y238	71.51
MAF	O75444	62.21
RNF6	Q9Y252	49.92

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 162. Enrichment computed across 10 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	1268.9×	0.026	TP53
TGFBR2 MSI Frameshift Mutants in Cancer	1	634.4×	0.026	TGFBR2
Regulation of TP53 Expression	1	634.4×	0.026	TP53
Loss of Function of TGFBR2 in Cancer	1	423.0×	0.026	TGFBR2
TGFBR2 Kinase Domain Mutants in Cancer	1	423.0×	0.026	TGFBR2
Impaired BRCA2 translocation to the nucleus	1	423.0×	0.026	BRCA2
Impaired BRCA2 binding to SEM1 (DSS1)	1	423.0×	0.026	BRCA2
PLCG1 events in ERBB2 signaling	1	317.2×	0.026	ERBB2
TGFBR1 LBD Mutants in Cancer	1	317.2×	0.026	TGFBR2
Transcriptional activation of cell cycle inhibitor p21	1	317.2×	0.026	TP53
Drug-mediated inhibition of ERBB2 signaling	1	317.2×	0.026	ERBB2
Resistance of ERBB2 KD mutants to trastuzumab	1	317.2×	0.026	ERBB2
Resistance of ERBB2 KD mutants to sapitinib	1	317.2×	0.026	ERBB2
Resistance of ERBB2 KD mutants to tesevatinib	1	317.2×	0.026	ERBB2
Resistance of ERBB2 KD mutants to neratinib	1	317.2×	0.026	ERBB2
Resistance of ERBB2 KD mutants to osimertinib	1	317.2×	0.026	ERBB2
Resistance of ERBB2 KD mutants to afatinib	1	317.2×	0.026	ERBB2
Resistance of ERBB2 KD mutants to AEE788	1	317.2×	0.026	ERBB2
Resistance of ERBB2 KD mutants to lapatinib	1	317.2×	0.026	ERBB2
Drug resistance in ERBB2 TMD/JMD mutants	1	317.2×	0.026	ERBB2
Loss of Function of TGFBR1 in Cancer	1	253.8×	0.027	TGFBR2
DSCAM interactions	1	253.8×	0.027	DCC
Activation of NOXA and translocation to mitochondria	1	211.5×	0.027	TP53
GRB7 events in ERBB2 signaling	1	211.5×	0.027	ERBB2
Loss of Function of SMAD2/3 in Cancer	1	211.5×	0.027	TGFBR2
Signaling by TGF-beta Receptor Complex in Cancer	1	211.5×	0.027	TGFBR2
SMAD2/3 Phosphorylation Motif Mutants in Cancer	1	211.5×	0.027	TGFBR2
TGFBR1 KD Mutants in Cancer	1	211.5×	0.027	TGFBR2
RUNX3 regulates CDKN1A transcription	1	181.3×	0.031	TP53
TGFBR3 regulates TGF-beta signaling	1	158.6×	0.034	TGFBR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 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 X-ray	2	177.4×	0.009	BRCA2, TP53
gastrulation	2	140.4×	0.009	TGFBR2, TP53
response to gamma radiation	2	116.2×	0.009	BRCA2, TP53
intrinsic apoptotic signaling pathway by p53 class mediator	2	116.2×	0.009	TP53, WWOX
positive regulation of reactive oxygen species metabolic process	2	102.1×	0.009	TGFBR2, TP53
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	2	99.1×	0.009	BRCA2, TP53
positive regulation of tolerance induction to self antigen	1	1685.2×	0.009	TGFBR2
positive regulation of B cell tolerance induction	1	1685.2×	0.009	TGFBR2
negative regulation of helicase activity	1	1685.2×	0.009	TP53
cellular response to actinomycin D	1	1685.2×	0.009	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	1685.2×	0.009	TP53
negative regulation of G1 to G0 transition	1	1685.2×	0.009	TP53
inferior endocardial cushion morphogenesis	1	1685.2×	0.009	TGFBR2
cellular response to ionizing radiation	2	82.2×	0.009	BRCA2, TP53
nucleotide-excision repair	2	76.6×	0.009	BRCA2, TP53
DNA damage response, signal transduction by p53 class mediator	2	71.7×	0.009	BRCA2, TP53
cellular response to growth factor stimulus	2	63.6×	0.009	TGFBR2, ERBB2
cellular senescence	2	59.1×	0.009	BRCA2, TP53
in utero embryonic development	3	21.6×	0.009	TGFBR2, TP53, MAF
positive regulation of mitochondrial membrane permeability	1	842.6×	0.013	TP53
bronchus morphogenesis	1	842.6×	0.013	TGFBR2
mammary gland morphogenesis	1	842.6×	0.013	TGFBR2
oligodendrocyte apoptotic process	1	842.6×	0.013	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	842.6×	0.013	TP53
negative regulation of pentose-phosphate shunt	1	842.6×	0.013	TP53
mitotic recombination-dependent replication fork processing	1	842.6×	0.013	BRCA2
double-strand break repair	2	40.6×	0.013	BRCA2, TP53
obsolete homolactic fermentation	1	561.7×	0.015	TP53
spinal cord ventral commissure morphogenesis	1	561.7×	0.015	DCC
adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway	1	561.7×	0.015	GNAS

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 7

Druggability breadth: 4 of 10 evidence-associated genes (40%) 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
ERBB2	CLOTRIMAZOLE
TGFBR2	PONATINIB
TP53	NITROFURANTOIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ERBB2	83	4
TGFBR2	22	4
DCC	0	0
RNF6	0	0
GNAS	0	0
BRCA2	0	0
WWOX	0	0
DLEC1	0	0
MAF	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	ERBB2, TP53
ERLOTINIB HYDROCHLORIDE	4	ERBB2
PONATINIB	4	ERBB2, TGFBR2
AFATINIB	4	ERBB2
LAPATINIB DITOSYLATE	4	ERBB2
SORAFENIB	4	ERBB2, TGFBR2
NERATINIB	4	ERBB2
IBRUTINIB	4	ERBB2
AFATINIB DIMALEATE	4	ERBB2
CABOZANTINIB	4	ERBB2
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2
VANDETANIB	4	ERBB2
TRIBROMSALAN	4	ERBB2
BOSUTINIB	4	ERBB2
BITHIONOL	4	ERBB2
ASTEMIZOLE	4	ERBB2, TP53
EBASTINE	4	ERBB2
OSIMERTINIB	4	ERBB2
BRIGATINIB	4	ERBB2
ACALABRUTINIB	4	ERBB2
ZANUBRUTINIB	4	ERBB2
TUCATINIB	4	ERBB2
TIRABRUTINIB	4	ERBB2
PACLITAXEL	4	ERBB2, TP53
LAZERTINIB	4	ERBB2
HEXACHLOROPHENE	4	ERBB2
DOXORUBICIN	4	ERBB2
DASATINIB	4	ERBB2, TGFBR2
ERLOTINIB	4	ERBB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
TGFBR2	188	Binding:188

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
TGFBR2	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ERBB2	1,221
TGFBR2	188
TP53	869

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

28 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)
CLOTRIMAZOLE	4	ERBB2, TP53
ERLOTINIB HYDROCHLORIDE	4	ERBB2
PONATINIB	4	ERBB2, TGFBR2
LAPATINIB DITOSYLATE	4	ERBB2
SORAFENIB	4	ERBB2, TGFBR2
NERATINIB	4	ERBB2
IBRUTINIB	4	ERBB2
AFATINIB DIMALEATE	4	ERBB2
CABOZANTINIB	4	ERBB2
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2
VANDETANIB	4	ERBB2
TRIBROMSALAN	4	ERBB2
BOSUTINIB	4	ERBB2
BITHIONOL	4	ERBB2
ASTEMIZOLE	4	ERBB2, TP53
EBASTINE	4	ERBB2
OSIMERTINIB	4	ERBB2
BRIGATINIB	4	ERBB2
ACALABRUTINIB	4	ERBB2
ZANUBRUTINIB	4	ERBB2
TUCATINIB	4	ERBB2
TIRABRUTINIB	4	ERBB2
PACLITAXEL	4	ERBB2, TP53
LAZERTINIB	4	ERBB2
HEXACHLOROPHENE	4	ERBB2
DOXORUBICIN	4	ERBB2
DASATINIB	4	ERBB2, TGFBR2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	ERBB2, TGFBR2, TP53
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	DCC
D	Druggable family + AlphaFold only, no drug	1	DLEC1
E	Difficult family or no structure, no drug	5	RNF6, GNAS, BRCA2, WWOX, MAF

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DCC	0	—
RNF6	0	—
GNAS	0	—
BRCA2	0	—
WWOX	0	—
DLEC1	0	—
MAF	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,301.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	407
PHASE2	312
PHASE1	164
PHASE1/PHASE2	94
PHASE3	81
PHASE4	19
PHASE2/PHASE3	17
EARLY_PHASE1	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT06437288	PHASE4	ENROLLING_BY_INVITATION	Hematoporphyrin Photodynamic Therapy for Esophageal Cancer
NCT07124351	PHASE4	RECRUITING	Intraoperative Imaging of Gastrointestinal Malignancies Using Pafolacianine (CYTALUX™)
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
NCT00754468	PHASE4	COMPLETED	Study of CryoSpray Ablation(TM)to Determine Treatment Effect, Depth of Injury, and Side Effects in the Esophagus.
NCT00790140	PHASE4	UNKNOWN	Trial of Enteral Nutrition Enriched With Eicosapentaenoic Acid (EPA) in Upper Gastrointestinal Cancer Surgery
NCT00911092	PHASE4	COMPLETED	Predictive Proteomic Factors of the Response to Concomitant Radiochemotherapy in Esophageal Cancer
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01416077	PHASE4	COMPLETED	Decreasing Postoperative Complications by Goal-Directed Fluid Therapy During Esophageal Resection
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT02042313	PHASE4	UNKNOWN	Postoperative Pain Management After Minimally Invasive Esophagectomy
NCT02320734	PHASE4	COMPLETED	Deep Neuromuscular Relaxation in Patients for Thoraco-laparoscopic Esophagectomy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03413436	PHASE4	COMPLETED	Lobaplation or Cisplatin in Adjuvant Chemotherapy for Esophageal Carcinoma
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT03731442	PHASE3	RECRUITING	Salvage Chemoradiation Therapy for Recurrence After Radical Surgery or Palliative Surgery in Esophageal Cancer Patients
NCT04135664	PHASE3	RECRUITING	Comparison of Esophagectomy and Chemoradiation for Patients With cN0-pT1b Stage Esophageal Squamous Cell Carcinoma
NCT04280822	PHASE3	RECRUITING	Neo-adjuvant Immunochemotheray Versus Neo-adjuvant Chemotherapy for Resectable Esophageal Carcinoma
NCT04415853	PHASE3	RECRUITING	Study of Larotinib in Unresectable Advanced or Recurrent Esophageal Cancer
NCT04513808	PHASE3	RECRUITING	Total Intravenous Anesthesia and Recurrence Free Survival
NCT04821778	PHASE3	RECRUITING	Chemoradiotherapy in Esophageal or Esophagogastric Junction Cancer
NCT04821843	PHASE3	RECRUITING	Neoadjuvant Treatment Modalities in Esophageal Cancer
NCT04871412	PHASE3	RECRUITING	The Thoracic Peri-Operative Integrative Surgical Care Evaluation Trial - Stage III
NCT05055648	PHASE3	RECRUITING	PROton Versus Photon Therapy for Esophageal Cancer - a Trimodality Strategy
NCT05188313	PHASE3	RECRUITING	TRAstuzumab and Pertuzumab for HER2+ Resectable Oesophageal Cancer
NCT05357846	PHASE3	RECRUITING	PD-1 Inhibitor Combined With Neoadjuvant Chemoradiotherapy Plus Surgery for Locally Advanced ESCC (NEOCRTEC2101)
NCT05504265	PHASE2/PHASE3	RECRUITING	Perioperative Analgesia Modes in Minimally Invasive Esophagectomy
NCT05547529	PHASE3	RECRUITING	The Efficacy of Neoadjuvant Chemoradiotherapy in Comparison With Neoadjuvant Chemotherapy in Patients With Resectable Squamous Cell Esophageal Cancer
NCT05865743	PHASE3	RECRUITING	Perioperative SDD to Prevent Infectious Complications After Esophagectomy
NCT06115629	PHASE3	NOT_YET_RECRUITING	Surveillance After Resection of Oesophageal aNd Gastric Cancer (SARONG-II) Trial
NCT06339060	PHASE3	RECRUITING	An Organ Preservation Strategies After Chemoradiotherapy Combined With Immunotherapy for Esophageal Cancer (PALACE3).
NCT06501664	PHASE3	NOT_YET_RECRUITING	Liposomal Irinotecan and 5-FU as Second-line Therapy for Patients With ESCC
NCT06782412	PHASE2/PHASE3	RECRUITING	Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
NCT06914011	PHASE3	NOT_YET_RECRUITING	Circulating Tumor DNA MRD-Guided Adjuvant Therapy for Curatively Resected Locally Advanced Esophageal Squamous Cell Carcinoma
NCT07000253	PHASE2/PHASE3	RECRUITING	Timing of Minimally Invasive Local Treatment After First-Line Systemic Therapy in Oligometastatic Esophageal or Gastric Adenocarcinoma
NCT07177794	PHASE3	RECRUITING	Consolidation of Toripalimab and Capecitabine After Chemoradiotherapy in ESCC

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IRINOTECAN	4	46
BEVACIZUMAB	4	8
EPIRUBICIN	4	8
CISPLATIN	4	6
ERLOTINIB	4	6
FLUOROURACIL	4	6
CETUXIMAB	4	3
FLOXURIDINE	4	3
HYDROXYUREA	4	3
LEUCOVORIN	4	3
NICOTINE	4	3
PANITUMUMAB	4	3
SUNITINIB MALATE	4	3
TORIPALIMAB	4	3
AFATINIB	4	2
EFLORNITHINE	4	2
FLUDEOXYGLUCOSE F 18	4	2
IXABEPILONE	4	2
RAMUCIRUMAB	4	2
SARGRAMOSTIM	4	2
TEGAFUR	4	2
VINORELBINE	4	2
ALDESLEUKIN	4	1
ARMODAFINIL	4	1
ARSENIC TRIOXIDE	4	1
ATEZOLIZUMAB	4	1
BUPROPION HYDROCHLORIDE	4	1
CAPECITABINE	4	1
CETIRIZINE	4	1
CITALOPRAM	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 8 predictive associations from 8 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
GNAS c.393T>C	Cisplatin + Fluorouracil	Resistance	CIViC B	EID2895
CDK9 Overexpression	Alvocidib + CAN508	Sensitivity/Response	CIViC D	EID9311
ERBB2 Amplification	Ibrutinib	Sensitivity/Response	CIViC D	EID6929
HDAC6 Overexpression	Panobinostat + Trichostatin A + Vorinostat	Sensitivity/Response	CIViC D	EID9856
HDAC9 Overexpression	HDAC Inhibitor REC-2282	Sensitivity/Response	CIViC D	EID9855
YAP1 Overexpression	Verteporfin	Sensitivity/Response	CIViC D	EID1983
YAP1 Overexpression	Docetaxel + Verteporfin	Sensitivity/Response	CIViC D	EID9329
YAP1 Overexpression	Docetaxel + Fluorouracil	Resistance	CIViC D	EID1982