Non-small cell lung carcinoma

Summary

Non-small cell lung carcinoma (MONDO:0005233) is a cancer caused by EGFR (GenCC Definitive), with 75 cohort genes (120 GWAS associations across 23 studies; 61 CIViC-evidence somatic drivers; 76 ClinVar predisposition records) and 5,061 clinical trials. The dominant Reactome pathway is RAF/MAP kinase cascade (20 cohort genes). Molecularly, ALK Fusion confers sensitivity to Alectinib in Lung Non-small Cell Carcinoma (CIViC Level A); 600 further subtype–drug associations are mapped below. Top therapeutic interventions include pemetrexed, erlotinib, and gefitinib.

At a glance

• Classification: Cancer
• Causal gene: EGFR (GenCC Definitive)
• Cohort genes: 75
• GWAS associations: 120
• ClinVar variants: 76
• Clinical trials: 5,061
• Precision-medicine evidence (CIViC): 601 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	non-small cell lung carcinoma
Mondo ID	MONDO:0005233
EFO	EFO:0003060
MeSH	D002289
Orphanet	488201
DOID	DOID:3908
NCIT	C2926
SNOMED CT	254637007
UMLS	C0007131
MedGen	40104
Is cancer (heuristic)	yes

Also known as: non-small cell cancer of lung · non-small cell cancer of the lung · non-small cell carcinoma of lung · non-small cell carcinoma of the lung · non-small cell lung cancer · non-small cell lung carcinoma · non-small cell lung carcinoma (disease) · NSCLC · NSCLC - non-small cell lung cancer

Data availability: 76 ClinVar variants · 120 GWAS associations (23 studies) · 1 GenCC gene-disease record · 1 HPO phenotype · 73 cell lines · 45 intOGen driver records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › lung carcinoma › non-small cell lung carcinoma

Related subtypes (9): bronchogenic carcinoma, asbestos-related lung carcinoma, lung hilum carcinoma, lung carcinoma in situ, squamous cell lung carcinoma, combined lung carcinoma, lung inflammatory myofibroblastic tumor, small cell lung carcinoma, lung epithelial-myoepithelial carcinoma

Subtypes (3): lung large cell carcinoma, lung adenocarcinoma, non-small cell squamous lung carcinoma

Genetics & variants

GWAS landscape

120 GWAS associations across 23 studies. Top hits map to 36 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs55781567	8e-44	CHRNA5	G	1.27
rs7705526	1e-42	TERT	A	1.2
rs4975538	8e-37	TERT	C	0.27
rs13167280	5e-32	TERT	A	1.24
rs11375254	3e-21	TPRG1 - TP63	T	1.21
rs2853677	4e-21	TERT	G	1.48
rs2378508	5e-21	TP63	C	0.28
rs13080835	1e-20	TP63	G	0.88
rs55768116	2e-13	MPZL3	C	1.1
rs4236709	1e-12	NRG1	G	1.12
rs7741164	4e-12	FOXP4-AS1	A	1.16
rs401681	8e-12	CLPTM1L	C	1.16
rs2517873	5e-11	MCCD1P1, HLA-H, HLA-H, POLR1HASP, POLR1HASP	A	1.16
rs12296850	1e-10	SLC17A8 - NR1H4	A	1.28
rs1853837	1e-10	FOXP4-AS1	A	1.12
rs2293607	2e-10	RNU6-637P - TERC	T	1.1
rs7086803	3e-10	VTI1A	A	1.14
rs10429489	7e-10	RN7SL151P - MTAP	A	1.11
rs12265047	8e-10	VTI1A	G	1.13
rs200595745	2e-09		A	1.09
rs147599930	2e-09	PLCL1	A	2.9
rs1200399	3e-09	BAZ1A	C	1.11
rs56113850	3e-09	CYP2A6	C	1.09
rs117979484	3e-09	NPAP1P6 - LINC01507	A	2.37
rs5879422	4e-09		T	1.08
rs34211819	4e-09	TNS3	A	0.73
rs1143149	1e-08	SEPTIN7	G	1.36
rs2131877	2e-08	XXYLT1	G	1.3
rs3769821	4e-08	CASP8	C	1.08
rs2439312	4e-08	NRG1	A	1.33

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST012199	Qin N	2020	27,120	27,355	Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma.
GCST008834	Dai J	2019	13,327	13,328	Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations.
GCST90301329	Fan J	2023	2,556	13,327	A two-stage genome-wide association study identified four potential early-onset nonsmall cell lung cancer risk loci based on 26,652 participants in Chinese population.
GCST005910	Li Y	2017	1,399	0	Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.
GCST90624807	Betti MJ	2025	1,385	3,590	Genetic analysis in African ancestry populations reveals genetic contributors to lung cancer susceptibility.
GCST90672021	Zhou D	2025	1,104	9,635	Non-coding genetic elements of lung cancer identified using whole genome sequencing in 13,722 Chinese.
GCST90132908	You D	2022	1,074	11,128	Associations of genetic risk, BMI trajectories, and the risk of non-small cell lung cancer: a population-based cohort study.
GCST001827	Dong J	2013	833	3,094	Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese.
GCST90315948	Lebrett MB	2023	652	0	Validation of lung cancer polygenic risk scores in a high-risk case-control cohort.
GCST000815	Yoon KA	2010	621	1,541	A genome-wide association study reveals susceptibility variants for non-small cell lung cancer in the Korean population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	3
Tier 3: regulatory	1
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	37
intergenic_variant	5
5_prime_UTR_variant	2
non_coding_transcript_exon_variant	2
unknown	2
regulatory_region_variant	1
splice_polypyrimidine_tract_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs55781567	15	78565644	C>G	0.32	5_prime_UTR_variant	CHRNA5	8e-44	Tier 2: splice/UTR
rs7705526	5	1285859	C>A,G,T	0.05	intron_variant	TERT	1e-42	Tier 4: intronic/intergenic
rs4975538	5	1280715	G>A,C,T	0.05	intron_variant	TERT	8e-37	Tier 4: intronic/intergenic
rs13167280	5	1280362	G>A,T	0.17	intron_variant	TERT	5e-32	Tier 4: intronic/intergenic
rs11375254	3	189625454	TAAA>T,TAA,TAAAA,TAAAAA,TAAAAAA	0.49	intron_variant	TPRG1 - TP63	3e-21	Tier 4: intronic/intergenic
rs2853677	5	1287079	G>A,C,T	0.05	intron_variant	TERT	4e-21	Tier 4: intronic/intergenic
rs2378508	3	189665991	T>A,C,G	0.05	intron_variant	TP63	5e-21	Tier 4: intronic/intergenic
rs13080835	3	189639410	G>T	0.05	intron_variant	TP63	1e-20	Tier 4: intronic/intergenic
rs55768116	11	118237616	C>A,G,T	0.489	intron_variant	MPZL3	2e-13	Tier 4: intronic/intergenic
rs4236709	8	32552592	G>A,C,T	0.198	intron_variant	NRG1	1e-12	Tier 4: intronic/intergenic
rs7741164	6	41525674	G>A	0.34	intron_variant	FOXP4-AS1	4e-12	Tier 4: intronic/intergenic
rs401681	5	1321972	C>T	0.32	intron_variant	CLPTM1L	8e-12	Tier 4: intronic/intergenic
rs2517873	6	29908215	G>A	0.145	intron_variant	MCCD1P1, HLA-H, HLA-H, POLR1HASP, POLR1HASP	5e-11	Tier 4: intronic/intergenic
rs12296850	12	100426307	A>G	0.256	intergenic_variant	SLC17A8 - NR1H4	1e-10	Tier 4: intronic/intergenic
rs1853837	6	41529297	C>A,G,T	0.258	intron_variant	FOXP4-AS1	1e-10	Tier 4: intronic/intergenic
rs2293607	3	169764547	T>A,C,G	0.404	non_coding_transcript_exon_variant	RNU6-637P - TERC	2e-10	Tier 4: intronic/intergenic
rs7086803	10	112738717	G>A	0.28	intron_variant	VTI1A	3e-10	Tier 4: intronic/intergenic
rs10429489	9	21787522	G>A,C	0.195	intron_variant	RN7SL151P - MTAP	7e-10	Tier 4: intronic/intergenic
rs12265047	10	112728166	G>A,C,T	0.243	intron_variant	VTI1A	8e-10	Tier 4: intronic/intergenic
rs200595745				0.43			2e-09	Tier 4: intronic/intergenic
rs147599930	2	198450969	C>A		intergenic_variant	PLCL1	2e-09	Tier 4: intronic/intergenic
rs1200399	14	34823979	C>T	0.405	intron_variant	BAZ1A	3e-09	Tier 4: intronic/intergenic
rs56113850	19	40847202	T>C	0.487	intron_variant	CYP2A6	3e-09	Tier 4: intronic/intergenic
rs117979484	9	79963383	T>A,C		intergenic_variant	NPAP1P6 - LINC01507	3e-09	Tier 4: intronic/intergenic
rs5879422				0.49			4e-09	Tier 4: intronic/intergenic
rs34211819	7	47499913	C>A,G,T	0.35	intron_variant	TNS3	4e-09	Tier 4: intronic/intergenic
rs1143149	7	35888665	C>G,T	0.34	intron_variant	SEPTIN7	1e-08	Tier 4: intronic/intergenic
rs2131877	3	195137645	G>A,C,T	0.44	intron_variant	XXYLT1	2e-08	Tier 4: intronic/intergenic
rs3769821	2	201258707	C>A,G,T	0.321	intron_variant	CASP8	4e-08	Tier 4: intronic/intergenic
rs2439312	8	32554841	A>C,G,T	0.05	intron_variant	NRG1	4e-08	Tier 4: intronic/intergenic

ClinVar germline variants

76 retrieved; paginated sample, class counts are floors:

30 pathogenic, 25 likely pathogenic, 11 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 2 not provided, 2 drug response, 1 pathogenic; drug response, 1 likely benign, 1 likely pathogenic; drug response

ClinVar	Variant (HGVS)	Gene	Classification	Review
13966	NM_004333.6(BRAF):c.1801A>G (p.Lys601Glu)	BRAF	Pathogenic	criteria provided, single submitter
13967	NM_004333.6(BRAF):c.1397G>T (p.Gly466Val)	BRAF	Pathogenic	no assertion criteria provided
13969	NM_004333.6(BRAF):c.1789C>G (p.Leu597Val)	BRAF	Pathogenic	criteria provided, multiple submitters, no conflicts
13971	NM_004333.6(BRAF):c.1406G>C (p.Gly469Ala)	BRAF	Pathogenic	criteria provided, single submitter
162793	NM_004333.6(BRAF):c.1794_1796dup (p.Thr599dup)	BRAF	Pathogenic	criteria provided, multiple submitters, no conflicts
177775	NM_004333.6(BRAF):c.1405G>A (p.Gly469Arg)	BRAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
40364	NM_004333.6(BRAF):c.1391G>T (p.Gly464Val)	BRAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
44801	NM_004333.6(BRAF):c.1396G>A (p.Gly466Arg)	BRAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
44802	NM_004333.6(BRAF):c.1405_1407del (p.Gly469del)	BRAF	Pathogenic	no assertion criteria provided
44803	NM_004333.6(BRAF):c.1406G>T (p.Gly469Val)	BRAF	Pathogenic	criteria provided, single submitter
16611	NM_005228.5(EGFR):c.2155G>T (p.Gly719Cys)	EGFR	Pathogenic; drug response	no assertion criteria provided
45220	NM_005228.5(EGFR):c.2127_2129del (p.Glu709_Thr710delinsAsp)	EGFR	Pathogenic	criteria provided, single submitter
45225	NM_005228.5(EGFR):c.2156G>C (p.Gly719Ala)	EGFR	Pathogenic	criteria provided, single submitter
45251	NM_005228.5(EGFR):c.2303G>T (p.Ser768Ile)	EGFR	Pathogenic	criteria provided, single submitter
45252	NM_005228.5(EGFR):c.2303_2304delinsTT (p.Ser768Ile)	EGFR	Pathogenic	criteria provided, single submitter
45257	NM_005228.5(EGFR):c.2310_2311insGGGTTG (p.Asp770_Asn771insGlyLeu)	EGFR	Pathogenic	no assertion criteria provided
45279	NM_005228.5(EGFR):c.2500G>T (p.Val834Leu)	EGFR	Pathogenic	criteria provided, single submitter
638163	NM_005228.5(EGFR):c.2303_2305delinsTCT (p.Ser768_Val769delinsIleLeu)	EGFR	Pathogenic	criteria provided, single submitter
45258	NM_005228.5(EGFR):c.2312_2314dup (p.Asn771_Pro772insHis)	EGFR-AS1	Pathogenic	criteria provided, single submitter
44992	NM_004448.4(ERBB2):c.2331_2339dup (p.Gly778_Pro780dup)	ERBB2	Pathogenic	criteria provided, single submitter
14721	NM_002198.3(IRF1):c.31T>C (p.Trp11Arg)	IRF1	Pathogenic	no assertion criteria provided
12579	NM_004985.5(KRAS):c.34G>C (p.Gly12Arg)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12580	NM_004985.5(KRAS):c.38G>A (p.Gly13Asp)	KRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
12582	NM_004985.5(KRAS):c.35G>A (p.Gly12Asp)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12583	NM_004985.5(KRAS):c.35G>T (p.Gly12Val)	KRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
12584	NM_004985.5(KRAS):c.34G>A (p.Gly12Ser)	KRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
12593	NM_004985.5(KRAS):c.37G>C (p.Gly13Arg)	KRAS	Pathogenic	criteria provided, single submitter
163766	NM_004985.5(KRAS):c.179G>T (p.Gly60Val)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
177777	NM_004985.5(KRAS):c.181C>A (p.Gln61Lys)	KRAS	Pathogenic	criteria provided, single submitter
45116	NM_004985.5(KRAS):c.182A>T (p.Gln61Leu)	KRAS	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 248 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
CDKN2A	CDKN2A	GWAS, Orphanet
TERT	TERT	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
EGFR	Act	BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC	CIViC #19
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
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
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
ETS2			CIViC #1763
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
NRAS	Act	ALL,AML,ANGS,CHOL,CLLSLL,COAD,COADREAD,GBM,HCC,LGGNOS,LUAD,LUSC,MEL,MGCT,NPC,OVT,PCM,PROSTATE,SKCM,THYM,UCEC,WDTC	CIViC #36
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
ROS1	LoF	HCC,HNSC,OVT,PRAD,STAD	CIViC #4941
RRM1			CIViC #5051
SMARCA4	Act	BL,BLADDER,BLCA,CCRCC,CHOL,COAD,COADREAD,EGC,ESCA,ESCC,HCC,HNSC,LGGNOS,LUAD,MBL,MLYM,NHL,NSCLC,OVT,PAAD,PANCREAS,PAST,PRCC,SACA,STAD,THYM	CIViC #78
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
AURKA			CIViC #61
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
TSC1	LoF	BLCA,BRCA,COADREAD,HCC,LUAD,RCC,SKCM,STAD,UTUC	CIViC #46
TYMS			CIViC #5971
WEE1			CIViC #6104
XRCC1			CIViC #6144
CBLB	Act	LUAD,NSCLC	CIViC #779
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
CD274	LoF	DLBCLNOS	CIViC #11335
PBK			CIViC #13276
HAVCR2			CIViC #16394
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52
KEAP1	Act	CHOL,HCC,LUAD,LUSC,NPC,NSCLC	CIViC #7777
CUL3	LoF	LUSC,PRCC,RCC	CIViC #6688
CXCR4	LoF	DLBCLNOS,MLYM,PAAD,PCM	CIViC #6329
DDR2	LoF	HCC	CIViC #51
ERBB3	Act	BLCA,BRCA,CESC,CHOL,COADREAD,NBL,PRAD,STAD,UCEC,UCS,UTUC	CIViC #1733

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
EGFR	Definitive	Autosomal dominant	lung cancer	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
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
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
NRAS	Orphanet:146	Differentiated thyroid carcinoma
NRAS	Orphanet:2612	Linear nevus sebaceus syndrome
NRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
NRAS	Orphanet:389	Langerhans cell histiocytosis
NRAS	Orphanet:626	Large/giant congenital melanocytic nevus
NRAS	Orphanet:648	Noonan syndrome
NRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation
PIK3CA	Orphanet:2495	Meningioma

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	17
civic_only	49
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	gencc,clinvar,civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar,civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	gwas,civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	clinvar,civic_evidence
ETS2	HGNC:3489	ENSG00000157557	P15036	Protein C-ets-2	gwas,civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar,civic_evidence
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	clinvar,civic_evidence
NRG1	HGNC:7997	ENSG00000157168	Q02297	Pro-neuregulin-1, membrane-bound isoform	gwas,civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar,civic_evidence
ROS1	HGNC:10261	ENSG00000047936	P08922	Proto-oncogene tyrosine-protein kinase ROS	civic_evidence
RRM1	HGNC:10451	ENSG00000167325	P23921	Ribonucleoside-diphosphate reductase large subunit	civic_evidence
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	civic_evidence
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	civic_evidence
AURKA	HGNC:11393	ENSG00000087586	O14965	Aurora kinase A	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	civic_evidence
TYMS	HGNC:12441	ENSG00000176890	P04818	Thymidylate synthase	civic_evidence
WEE1	HGNC:12761	ENSG00000166483	P30291	Wee1-like protein kinase	civic_evidence
XRCC1	HGNC:12828	ENSG00000073050	P18887	DNA repair protein XRCC1	civic_evidence
CBLB	HGNC:1542	ENSG00000114423	Q13191	E3 ubiquitin-protein ligase CBL-B	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
PBK	HGNC:18282	ENSG00000168078	Q96KB5	Lymphokine-activated killer T-cell-originated protein kinase	civic_evidence
HAVCR2	HGNC:18437	ENSG00000135077	Q8TDQ0	Hepatitis A virus cellular receptor 2	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
KEAP1	HGNC:23177	ENSG00000079999	Q14145	Kelch-like ECH-associated protein 1	civic_evidence
CUL3	HGNC:2553	ENSG00000036257	Q13618	Cullin-3	civic_evidence
CXCR4	HGNC:2561	ENSG00000121966	P61073	C-X-C chemokine receptor type 4	civic_evidence
DDR2	HGNC:2731	ENSG00000162733	Q16832	Discoidin domain-containing receptor 2	civic_evidence
ERBB3	HGNC:3431	ENSG00000065361	P21860	Receptor tyrosine-protein kinase erbB-3	civic_evidence
ERCC1	HGNC:3433	ENSG00000012061	P07992	DNA excision repair protein ERCC-1	civic_evidence
ERCC2	HGNC:3434	ENSG00000104884	P18074	General transcription and DNA repair factor IIH helicase subunit XPD	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
ABCB1	HGNC:40	ENSG00000085563	P08183	ATP-dependent translocase ABCB1	civic_evidence
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	civic_evidence
GNAS	HGNC:4392	ENSG00000087460	O95467	Neuroendocrine secretory protein 55	civic_evidence
ABCC10	HGNC:52	ENSG00000124574	Q5T3U5	ATP-binding cassette sub-family C member 10	civic_evidence
IGF1R	HGNC:5465	ENSG00000140443	P08069	Insulin-like growth factor 1 receptor	civic_evidence
BIRC5	HGNC:593	ENSG00000089685	O15392	Baculoviral IAP repeat-containing protein 5	civic_evidence
JAK1	HGNC:6190	ENSG00000162434	P23458	Tyrosine-protein kinase JAK1	civic_evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence
ARAF	HGNC:646	ENSG00000078061	P10398	Serine/threonine-protein kinase A-Raf	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
ABL1	HGNC:76	ENSG00000097007	P00519	Tyrosine-protein kinase ABL1	civic_evidence
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	civic_evidence
NFE2L2	HGNC:7782	ENSG00000116044	Q16236	Nuclear factor erythroid 2-related factor 2	civic_evidence
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	civic_evidence
NTRK1	HGNC:8031	ENSG00000198400	P04629	High affinity nerve growth factor receptor	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
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.
ETS2	Protein C-ets-2	Transcription factor activating transcription.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
NRAS	GTPase NRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
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.
ROS1	Proto-oncogene tyrosine-protein kinase ROS	Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium.
RRM1	Ribonucleoside-diphosphate reductase large subunit	Provides the precursors necessary for DNA synthesis.
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
AURKA	Aurora kinase A	Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TSC1	Hamartin	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…
TYMS	Thymidylate synthase	Catalyzes the reductive methylation of 2’-deoxyuridine 5’-monophosphate (dUMP) to thymidine 5’-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to…
WEE1	Wee1-like protein kinase	Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on ‘Tyr-15’.
XRCC1	DNA repair protein XRCC1	Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes.
CBLB	E3 ubiquitin-protein ligase CBL-B	E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome.
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.
PBK	Lymphokine-activated killer T-cell-originated protein kinase	Phosphorylates MAP kinase p38.
HAVCR2	Hepatitis A virus cellular receptor 2	Cell surface receptor implicated in modulating innate and adaptive immune responses.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
KEAP1	Kelch-like ECH-associated protein 1	Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination.
CUL3	Cullin-3	Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins.
CXCR4	C-X-C chemokine receptor type 4	Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation.
DDR2	Discoidin domain-containing receptor 2	Tyrosine kinase involved in the regulation of tissues remodeling.
ERBB3	Receptor tyrosine-protein kinase erbB-3	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.
ERCC1	DNA excision repair protein ERCC-1	Non-catalytic component of a structure-specific DNA repair endonuclease responsible for the 5’-incision during DNA repair.
ERCC2	General transcription and DNA repair factor IIH helicase subunit XPD	ATP-dependent 5’-3’ DNA helicase.
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.
ABCB1	ATP-dependent translocase ABCB1	Translocates drugs and phospholipids across the membrane.
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.
ABCC10	ATP-binding cassette sub-family C member 10	ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells.
IGF1R	Insulin-like growth factor 1 receptor	Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1).
BIRC5	Baculoviral IAP repeat-containing protein 5	Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis.
JAK1	Tyrosine-protein kinase JAK1	Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
ARAF	Serine/threonine-protein kinase A-Raf	Involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
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.
ABL1	Tyrosine-protein kinase ABL1	Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autopha…
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
NFE2L2	Nuclear factor erythroid 2-related factor 2	Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes the…
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.
NTRK1	High affinity nerve growth factor receptor	Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons.
NTRK3	NT-3 growth factor receptor	Receptor tyrosine kinase involved in nervous system and probably heart development.

Protein-family classification

Druggable: 41 · Difficult: 11 · Unknown: 23 · Druggable fraction: 0.55

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	26	9.6×	3e-18
Transporter	4	4.2×	0.072
Ion channel	1	1.5×	0.930
Antibody/Immunoglobulin	3	1.2×	0.930
Scaffold/PPI	4	0.9×	0.930
Enzyme (other)	5	0.8×	0.930
Transcription factor	7	0.8×	0.930
GPCR	2	0.6×	0.930
Other/Unknown	23	0.6×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ETS2	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
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
ROS1	Kinase	yes	2.7.10.1	LDLR_classB_rpt, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
RRM1	Enzyme (other)	yes	1.17.4.1	RNR_lg_C, ATP-cone_dom, RNR_R1-su_N
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
AURKA	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
TSC1	Other/Unknown	no		Hamartin
TYMS	Enzyme (other)	yes	2.1.1.45	Thymidylate_synthase, Thymidylate_synthase_AS, Thymidate_synth/dCMP_Mease_dom
WEE1	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
XRCC1	Other/Unknown	no		BRCT_dom, Xrcc1_N, Galactose-bd-like_sf
CBLB	Transcription factor	no		Znf_RING, Adaptor_Cbl_N_hlx, EF-hand-dom_pair
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
PBK	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
HAVCR2	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
KEAP1	Other/Unknown	no		BTB/POZ_dom, Kelch_1, SKP1/BTB/POZ_sf
CUL3	Other/Unknown	no		Cullin_N, Cullin_CS, Cullin_homology
CXCR4	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, CXCR4/ACKR2
DDR2	Kinase	yes	2.7.10.1	FA58C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB3	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERCC1	Other/Unknown	no		ERCC1/RAD10/SWI10, RuvA_2-like, Restrct_endonuc-II-like
ERCC2	Enzyme (other)	yes	3.6.4.12	RAD3/XPD, DNA/RNA_helicase_DEAH_CS, Helicase-like_DEXD_c2
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
ABCB1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
GNAS	Other/Unknown	no		NESP55, Gprotein_alpha_S, Gprotein_alpha_su
ABCC10	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
IGF1R	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
BIRC5	Other/Unknown	no		BIR_rpt, Baculoviral_IAP
JAK1	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
ARAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
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
ABL1	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot
NFE2L2	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
NTRK1	Kinase	yes	2.7.10.1	Cys-rich_flank_reg_C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

72 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)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	13
calcaneal tendon	9
ganglionic eminence	8
secondary oocyte	5
male germ line stem cell (sensu Vertebrata) in testis	5
colonic epithelium	4
stromal cell of endometrium	4
male germ cell	4
sperm	4
dorsal root ganglion	4
Brodmann (1909) area 23	4
nipple	3
buccal mucosa cell	3
cervix squamous epithelium	3
sural nerve	3
trigeminal ganglion	3
epithelium of nasopharynx	3
oocyte	3
adrenal tissue	3
corpus epididymis	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
ETS2	287	ubiquitous	marker	skin of abdomen, mucosa of urinary bladder, skin of leg
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
NRAS	278	ubiquitous	marker	gingival epithelium, epithelium of nasopharynx, secondary oocyte
NRG1	209	ubiquitous	marker	ventricular zone, ganglionic eminence, oocyte
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
ROS1	79	tissue_specific	marker	upper lobe of left lung, upper lobe of lung, corpus epididymis
RRM1	296	ubiquitous	marker	ventricular zone, ganglionic eminence, cervix squamous epithelium
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
AURKA	236	ubiquitous	marker	oocyte, secondary oocyte, ventricular zone
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
TSC1	297	ubiquitous	marker	substantia nigra pars compacta, gluteal muscle, lateral globus pallidus
TYMS	262	ubiquitous	marker	ventricular zone, embryo, trabecular bone tissue
WEE1	262	ubiquitous	marker	ventricular zone, upper leg skin, mucosa of paranasal sinus
XRCC1	276	ubiquitous	marker	ventricular zone, tendon of biceps brachii, ganglionic eminence
CBLB	274	ubiquitous	marker	pericardium, colonic epithelium, calcaneal tendon
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung
PBK	189	ubiquitous	marker	ventricular zone, sperm, male germ cell
HAVCR2	206	broad	marker	granulocyte, leukocyte, monocyte
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
KEAP1	294	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, muscle of leg
CUL3	296	ubiquitous	marker	sperm, male germ cell, left testis
CXCR4	281	ubiquitous	marker	bone marrow, thymus, lymph node
DDR2	270	ubiquitous	marker	cauda epididymis, tendon of biceps brachii, vena cava
ERBB3	274	broad	marker	trigeminal ganglion, jejunal mucosa, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 121.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
KRAS	14,509
CUL3	9,954
ERBB2	9,659
CDKN2A	9,311
NTRK1	9,181
CCND1	8,328
SMARCA4	8,138
MAPK1	8,003

Intra-cohort edges

A	B	Sources
ABCB1	ABCC10	string_interaction
ABL1	EGFR	intact
ABL1	RB1	biogrid_interaction
ABL1	TP53	string_interaction
ALK	CD274	string_interaction
ALK	KRAS	string_interaction
ALK	NRAS	string_interaction
ALK	RET	intact
ANKS1A	EGFR	intact
ANKS1A	RB1	biogrid_interaction
ARAF	BRAF	biogrid_interaction, intact
ARAF	KRAS	biogrid_interaction, intact
ARAF	NRAS	intact
AREG	EGFR	intact, string_interaction
AREG	ERBB2	string_interaction
AREG	ERBB3	string_interaction
AURKA	BIRC5	string_interaction
AURKA	EGFR	intact
AURKA	TP53	string_interaction
BCL2L11	TP53	string_interaction
BIRC5	PBK	string_interaction
BRAF	CDKN2A	string_interaction
BRAF	EGFR	biogrid_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MAPK1	biogrid_interaction
BRAF	NF1	string_interaction
BRAF	NRAS	biogrid_interaction, intact, string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	ROS1	intact
BRAF	TP53	string_interaction
BRAF	WEE1	intact
CBLB	DDR2	biogrid_interaction, intact
CBLB	NTRK1	biogrid_interaction
CCND1	CDKN2A	biogrid_interaction, string_interaction
CCND1	RB1	string_interaction
CCND1	TP53	string_interaction
CD274	HAVCR2	string_interaction
CD274	ROS1	string_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	RB1	string_interaction
CDKN2A	TP53	string_interaction
CDKN2A	TP63	string_interaction
CUL3	DDR2	intact
CUL3	GNAS	intact
CUL3	KEAP1	string_interaction
CUL3	NFE2L2	string_interaction
CXCR4	JAK1	intact
CXCR4	NTRK3	biogrid_interaction
DDR2	EGFR	string_interaction
DDR2	KRAS	string_interaction

Structural data

PDB: 65 · AlphaFold-only: 10 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
GNAS	O95467	490
EGFR	P00533	388
TP53	P04637	313
AURKA	O14965	193
PIM1	P11309	191
MAPK1	P28482	160
PIK3CA	P42336	135
BRAF	P15056	131
KEAP1	Q14145	122
ABL1	P00519	85
FGFR1	P11362	83
ALK	Q9UM73	79
CD274	Q9NZQ7	76
NTRK1	P04629	65
ERBB2	P04626	63
TYMS	P04818	61
KIT	P10721	52
ERCC2	P18074	51
JAK1	P23458	51
IGF1R	P08069	46
BCL2L11	O43521	45
BIRC5	O15392	36
CASP8	Q14790	36
NRAS	P01111	35
RET	P07949	34
CXCR4	P61073	33
SMARCA4	P51532	31
CUL3	Q13618	30
WEE1	P30291	29

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC35D2	Q76EJ3	85.58
VTI1A	Q96AJ9	85.00
APCDD1	Q8J025	82.10
CHRNA5	P30532	82.04
ABCC10	Q5T3U5	81.32
SLC17A8	Q8NDX2	77.81
CDH8	P55286	77.26
ADGRF3	Q8IZF5	74.07
SCYL2	Q6P3W7	71.63
SLTM	Q9NWH9	52.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 882. Enrichment computed across 100 evidence-associated genes (80 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 80 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	20	15.3×	9e-16	EGFR, BRAF, ERBB2, KRAS, NRAS, NRG1, PIK3CA, CAMK2D (+12 more)
Signaling by ERBB2 KD Mutants	8	42.3×	4e-09	EGFR, ERBB2, KRAS, NRAS, NRG1, PIK3CA, ERBB3, HRAS
SHC1 events in ERBB2 signaling	7	41.6×	4e-08	EGFR, ERBB2, KRAS, NRAS, NRG1, ERBB3, HRAS
Signaling by ERBB2 TMD/JMD mutants	7	41.6×	4e-08	EGFR, ERBB2, KRAS, NRAS, NRG1, ERBB3, HRAS
Signaling by RAF1 mutants	8	27.9×	6e-08	BRAF, KRAS, NRAS, CAMK2D, HRAS, ARAF, MAP2K1, MAPK1
Signaling by moderate kinase activity BRAF mutants	8	25.4×	6e-08	BRAF, KRAS, NRAS, CAMK2D, HRAS, ARAF, MAP2K1, MAPK1
Paradoxical activation of RAF signaling by kinase inactive BRAF	8	25.4×	6e-08	BRAF, KRAS, NRAS, CAMK2D, HRAS, ARAF, MAP2K1, MAPK1
Signaling downstream of RAS mutants	8	25.4×	6e-08	BRAF, KRAS, NRAS, CAMK2D, HRAS, ARAF, MAP2K1, MAPK1
Constitutive Signaling by Aberrant PI3K in Cancer	10	15.9×	6e-08	EGFR, ERBB2, NRG1, PIK3CA, ERBB3, FGFR1, KIT, AREG (+2 more)
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	11	13.3×	6e-08	EGFR, ERBB2, NRG1, PIK3CA, ERBB3, FGFR1, KIT, AREG (+3 more)
Signaling by BRAF and RAF1 fusions	9	19.2×	6e-08	BRAF, KRAS, NRAS, CAMK2D, HRAS, ARAF, MAP2K1, MAPK1 (+1 more)
Signaling by ERBB2 ECD mutants	6	50.4×	8e-08	EGFR, ERBB2, KRAS, NRAS, PIK3CA, HRAS
GRB2 events in ERBB2 signaling	6	47.6×	1e-07	EGFR, ERBB2, KRAS, NRAS, NRG1, HRAS
RAF activation	7	29.4×	2e-07	BRAF, KRAS, NRAS, CAMK2D, HRAS, ARAF, MAP2K1
Signaling by high-kinase activity BRAF mutants	7	27.8×	3e-07	BRAF, KRAS, NRAS, HRAS, ARAF, MAP2K1, MAPK1
MAPK family signaling cascades	10	12.9×	3e-07	BRAF, CAMK2D, SEPTIN7, JAK1, KIT, ARAF, AREG, MAP2K1 (+2 more)
MAPK1/MAPK3 signaling	9	14.8×	4e-07	BRAF, CAMK2D, JAK1, KIT, ARAF, AREG, MAP2K1, MAPK1 (+1 more)
MAP2K and MAPK activation	7	25.0×	5e-07	BRAF, KRAS, NRAS, HRAS, ARAF, MAP2K1, MAPK1
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	5	54.9×	8e-07	KRAS, NRAS, PIK3CA, HRAS, PDGFRA
Signaling by PDGFRA extracellular domain mutants	5	54.9×	8e-07	KRAS, NRAS, PIK3CA, HRAS, PDGFRA
Negative regulation of MAPK pathway	7	23.2×	8e-07	BRAF, KRAS, NRAS, HRAS, ARAF, MAP2K1, MAPK1
Oncogenic MAPK signaling	7	21.7×	1e-06	BRAF, CAMK2D, ARAF, MAP2K1, MAPK1, NF1, BCL2L11
PIP3 activates AKT signaling	11	9.2×	1e-06	EGFR, ERBB2, NRG1, PIK3CA, ERBB3, FGFR1, KIT, AREG (+3 more)
GRB2 events in EGFR signaling	5	47.6×	2e-06	EGFR, KRAS, NRAS, HRAS, AREG
Downstream signal transduction	6	28.6×	2e-06	KRAS, NRAS, PIK3CA, HRAS, PDGFRA, RASA1
SHC1 events in EGFR signaling	5	44.6×	2e-06	EGFR, KRAS, NRAS, HRAS, AREG
Constitutive Signaling by EGFRvIII	5	44.6×	2e-06	EGFR, KRAS, NRAS, PIK3CA, HRAS
RAS signaling downstream of NF1 loss-of-function variants	4	81.6×	2e-06	KRAS, NRAS, HRAS, NF1
Estrogen-stimulated signaling through PRKCZ	4	81.6×	2e-06	KRAS, NRAS, HRAS, MAPK1
PI3K events in ERBB2 signaling	5	42.0×	3e-06	EGFR, ERBB2, NRG1, PIK3CA, ERBB3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 97 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Schwann cell development	6	65.2×	2e-07	ERBB2, ERBB3, HRAS, MAP2K1, MAPK1, NF1
cell surface receptor protein tyrosine kinase signaling pathway	10	17.9×	2e-07	ERBB2, NRG1, ROS1, DDR2, ERBB3, ALK, NTRK1, NTRK3 (+2 more)
MAPK cascade	10	15.8×	4e-07	BRAF, KRAS, NRAS, FGFR1, HRAS, ARAF, MAP2K1, MAPK1 (+2 more)
ERBB2-ERBB3 signaling pathway	5	86.9×	5e-07	ERBB2, NRG1, ERBB3, MAP2K1, MAPK1
protein autophosphorylation	10	15.0×	5e-07	STK11, AURKA, DDR2, FGFR1, ALK, IGF1R, KIT, NTRK1 (+2 more)
neuron apoptotic process	9	17.2×	7e-07	KRAS, TP53, TP63, ERBB3, HRAS, ABL1, NF1, NTRK1 (+1 more)
epidermal growth factor receptor signaling pathway	8	20.4×	1e-06	EGFR, BRAF, ERBB2, PIK3CA, ERBB3, AREG, MAPK1, ABL1
positive regulation of ERK1 and ERK2 cascade	11	9.7×	4e-06	EGFR, BRAF, NRG1, HAVCR2, DDR2, HRAS, MAP2K1, ABL1 (+3 more)
insulin-like growth factor receptor signaling pathway	6	30.7×	7e-06	PIK3CA, ERCC1, ERCC2, IGF1R, MAP2K1, MAPK1
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	11	8.9×	7e-06	EGFR, PIK3CA, DDR2, ERBB3, FGFR1, IGF1R, KIT, NTRK1 (+3 more)
protein phosphorylation	11	7.7×	3e-05	BRAF, ERBB2, ROS1, STK11, AURKA, CAMK2D, FGFR1, JAK1 (+3 more)
negative regulation of neuron apoptotic process	9	10.3×	3e-05	BRAF, KRAS, PIK3CA, TERT, CCND1, ERBB3, HRAS, NTRK1 (+1 more)
Ras protein signal transduction	7	14.8×	6e-05	CDKN2A, KRAS, NRAS, TP53, HRAS, NF1, RB1
positive regulation of cell migration	11	7.0×	6e-05	EGFR, CASP8, CXCR4, HRAS, IGF1R, KIT, MAP2K1, NOTCH1 (+3 more)
negative regulation of apoptotic process	14	5.0×	8e-05	EGFR, BRAF, ERBB2, AURKA, TP53, DDR2, ERBB3, IGF1R (+6 more)
cellular senescence	6	18.3×	9e-05	CDKN2A, TP53, TP63, HRAS, MAP2K1, ABL1
replicative senescence	4	40.9×	2e-04	CDKN2A, TERT, TP53, ERCC1
myelination	6	15.6×	2e-04	ERBB2, TSC1, ERBB3, HRAS, MAP2K1, MAPK1
peptidyl-tyrosine phosphorylation	5	21.7×	3e-04	ERBB2, DDR2, FGFR1, NTRK1, PDGFRA
positive regulation of MAPK cascade	9	7.5×	3e-04	EGFR, ERBB2, ERBB3, FGFR1, HRAS, IGF1R, KIT, NTRK3 (+1 more)
endocardial cell differentiation	3	86.9×	3e-04	NRG1, SMAD4, NOTCH1
glial cell proliferation	4	36.6×	3e-04	KRAS, TP53, AREG, RB1
T cell receptor signaling pathway	7	11.0×	3e-04	BRAF, PIK3CA, STK11, CBLB, HRAS, MAPK1, ABL1
positive regulation of G1/S transition of mitotic cell cycle	5	20.7×	3e-04	EGFR, RRM1, TERT, CCND1, DDR2
positive regulation of cell population proliferation	13	4.5×	4e-04	EGFR, NRG1, SMARCA4, CUL3, FGFR1, HRAS, IGF1R, BIRC5 (+5 more)
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	13.0×	4e-04	EGFR, ERBB2, PIK3CA, ERBB3, IGF1R, NF1
thymus development	5	17.4×	6e-04	BRAF, MAP2K1, MAPK1, ABL1, BCL2L11
ERK1 and ERK2 cascade	5	16.4×	8e-04	BRAF, SMAD4, MAP2K1, MAPK1, ABL1
stem cell proliferation	5	16.1×	8e-04	TP53, TP63, FGFR1, ABCB1, NF1
peptidyl-tyrosine autophosphorylation	3	57.9×	8e-04	ALK, IGF1R, NTRK1

Therapeutics

Drugs indicated for this disease

25 approved, 142 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Adagrasib	Approved (phase 4)
Amivantamab	Approved (phase 4)
Atezolizumab	Approved (phase 4)
Bevacizumab	Approved (phase 4)
Brigatinib	Approved (phase 4)
Ceritinib	Approved (phase 4)
Crizotinib	Approved (phase 4)
Docetaxel Anhydrous	Approved (phase 4)
Durvalumab	Approved (phase 4)
Entrectinib	Approved (phase 4)
Gefitinib	Approved (phase 4)
Ipilimumab	Approved (phase 4)
Lorlatinib	Approved (phase 4)
Necitumumab	Approved (phase 4)
Nivolumab	Approved (phase 4)
Paclitaxel	Approved (phase 4)
Pembrolizumab	Approved (phase 4)
Pralsetinib	Approved (phase 4)
Ramucirumab	Approved (phase 4)
Selpercatinib	Approved (phase 4)
Sotorasib	Approved (phase 4)
Sugemalimab	Approved (phase 4)
Tislelizumab	Approved (phase 4)
Tremelimumab	Approved (phase 4)
Zenocutuzumab	Approved (phase 4)
ASK-120067	Phase 3 (in late-stage trials)
Abemaciclib	Phase 3 (in late-stage trials)
Abivertinib	Phase 3 (in late-stage trials)
Acetylcarnitine	Phase 3 (in late-stage trials)
Afatinib	Phase 3 (in late-stage trials)
Alectinib	Phase 3 (in late-stage trials)
Aprepitant	Phase 3 (in late-stage trials)
Aprinocarsen	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Astuprotimut-R	Phase 3 (in late-stage trials)
Aumolertinib	Phase 3 (in late-stage trials)
Avelumab	Phase 3 (in late-stage trials)
Bavituximab	Phase 3 (in late-stage trials)
Belrestotug	Phase 3 (in late-stage trials)
Benmelstobart	Phase 3 (in late-stage trials)
Bexarotene	Phase 3 (in late-stage trials)
Bintrafusp Alfa	Phase 3 (in late-stage trials)
Bupivacaine	Phase 3 (in late-stage trials)
Cabozantinib	Phase 3 (in late-stage trials)
Cadonilimab	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Canakinumab	Phase 3 (in late-stage trials)
Capecitabine	Phase 3 (in late-stage trials)
Capmatinib	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Carboxyamidotriazole	Phase 3 (in late-stage trials)
Catequentinib	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Cemiplimab	Phase 3 (in late-stage trials)
Ceralasertib	Phase 3 (in late-stage trials)
Cetuximab	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Cobalamin	Phase 3 (in late-stage trials)
Cosibelimab	Phase 3 (in late-stage trials)
Custirsen	Phase 3 (in late-stage trials)
Dacomitinib Anhydrous	Phase 3 (in late-stage trials)
Datopotamab Deruxtecan	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Domvanalimab	Phase 3 (in late-stage trials)
Dostarlimab	Phase 3 (in late-stage trials)
Endostatin	Phase 3 (in late-stage trials)
Endostatin, N-Terminal-Mggshhhhh	Phase 3 (in late-stage trials)
Enobosarm	Phase 3 (in late-stage trials)
Enoxaparin Sodium	Phase 3 (in late-stage trials)
Ensartinib	Phase 3 (in late-stage trials)
Epinephrine	Phase 3 (in late-stage trials)
Erfonrilimab	Phase 3 (in late-stage trials)
Eribulin	Phase 3 (in late-stage trials)
Erlotinib	Phase 3 (in late-stage trials)
Erythromycin	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Exisulind	Phase 3 (in late-stage trials)
Famitinib	Phase 3 (in late-stage trials)
Figitumumab	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Firmonertinib	Phase 3 (in late-stage trials)
Folic Acid	Phase 3 (in late-stage trials)
Fruquintinib	Phase 3 (in late-stage trials)
Fusidic Acid	Phase 3 (in late-stage trials)
Ganetespib	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Gossypol	Phase 3 (in late-stage trials)
Hyaluronidase	Phase 3 (in late-stage trials)
Hyaluronidase (Human Recombinant)	Phase 3 (in late-stage trials)
Icotinib	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Ivonescimab	Phase 3 (in late-stage trials)
Lazertinib	Phase 3 (in late-stage trials)
Lenvatinib	Phase 3 (in late-stage trials)
Linrodostat	Phase 3 (in late-stage trials)
Lonafarnib	Phase 3 (in late-stage trials)
Loperamide	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Mitomycin	Phase 3 (in late-stage trials)
Mobocertinib	Phase 3 (in late-stage trials)
Monalizumab	Phase 3 (in late-stage trials)
Motesanib	Phase 3 (in late-stage trials)
Napabucasin	Phase 3 (in late-stage trials)
Nedaplatin	Phase 3 (in late-stage trials)
Nintedanib	Phase 3 (in late-stage trials)
Niraparib	Phase 3 (in late-stage trials)
Nogapendekin Alfa	Phase 3 (in late-stage trials)
Ociperlimab	Phase 3 (in late-stage trials)
Olaparib	Phase 3 (in late-stage trials)
Oleclumab	Phase 3 (in late-stage trials)
Onartuzumab	Phase 3 (in late-stage trials)
Opnurasib	Phase 3 (in late-stage trials)
Osimertinib	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Oxiglutatione	Phase 3 (in late-stage trials)
P-Toluenesulfonamide	Phase 3 (in late-stage trials)
Paclitaxel Docosahexaenoic Acid	Phase 3 (in late-stage trials)
Paclitaxel Poliglumex	Phase 3 (in late-stage trials)
Patritumab	Phase 3 (in late-stage trials)
Pegfilgrastim	Phase 3 (in late-stage trials)
Pemetrexed	Phase 3 (in late-stage trials)
Platinum	Phase 3 (in late-stage trials)
Plinabulin	Phase 3 (in late-stage trials)
Poziotinib	Phase 3 (in late-stage trials)
Pyrotinib	Phase 3 (in late-stage trials)
Racotumomab	Phase 3 (in late-stage trials)
Repotrectinib	Phase 3 (in late-stage trials)
Retifanlimab	Phase 3 (in late-stage trials)
Retlirafusp Alfa	Phase 3 (in late-stage trials)
Rezivertinib	Phase 3 (in late-stage trials)
Rilvegostomig	Phase 3 (in late-stage trials)
Rivoceranib	Phase 3 (in late-stage trials)
Rociletinib	Phase 3 (in late-stage trials)
Sacituzumab Govitecan	Phase 3 (in late-stage trials)
Sacituzumab Tirumotecan	Phase 3 (in late-stage trials)
Savolitinib	Phase 3 (in late-stage trials)
Selumetinib	Phase 3 (in late-stage trials)
Serplulimab	Phase 3 (in late-stage trials)
Sigvotatug Vedotin	Phase 3 (in late-stage trials)
Sintilimab	Phase 3 (in late-stage trials)
Sitravatinib	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Sorafenib	Phase 3 (in late-stage trials)
Sunitinib	Phase 3 (in late-stage trials)
Sunvozertinib	Phase 3 (in late-stage trials)
Talabostat	Phase 3 (in late-stage trials)
Talactoferrin Alfa	Phase 3 (in late-stage trials)
Tariquidar	Phase 3 (in late-stage trials)
Tecemotide	Phase 3 (in late-stage trials)
Telisotuzumab Vedotin	Phase 3 (in late-stage trials)
Temozolomide	Phase 3 (in late-stage trials)
Tertomotide	Phase 3 (in late-stage trials)
Tesevatinib	Phase 3 (in late-stage trials)
Tinzaparin Sodium	Phase 3 (in late-stage trials)
Tiragolumab	Phase 3 (in late-stage trials)
Tivantinib	Phase 3 (in late-stage trials)
Topotecan	Phase 3 (in late-stage trials)
Toripalimab	Phase 3 (in late-stage trials)
Trastuzumab Deruxtecan	Phase 3 (in late-stage trials)
Tretinoin	Phase 3 (in late-stage trials)
Tusamitamab Ravtansine	Phase 3 (in late-stage trials)
Vadimezan	Phase 3 (in late-stage trials)
Vandetanib	Phase 3 (in late-stage trials)
Veliparib	Phase 3 (in late-stage trials)
Vibostolimab	Phase 3 (in late-stage trials)
Vinorelbine	Phase 3 (in late-stage trials)
Zimberelimab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Acalabrutinib, Acetaminophen, Adebrelimab, Aglatimagene Besadenovec, Alclometasone Dipropionate, Aldoxorubicin, Anamorelin, Artenimol, Ascorbic Acid, Avutometinib, Axitinib, Azacitidine, Becotatug Vedotin, Belotecan, Binimetinib, Bortezomib, Buparlisib, CLN-081, CM-082, Cabazitaxel, Capivasertib, Cediranib, Chlorhexidine, Cilengitide, Cirmtuzumab, Clarithromycin, Clindamycin, Cobimetinib, Cyanocobalamin, Dabrafenib, Dapsone, Daratumumab, Dasatinib Anhydrous, Decitabine, Defactinib, Denosumab, Desloratadine, Digoxin, Diphenhydramine, Disulfiram, Dovitinib, Doxorubicin, Encorafenib, Entinostat, Envafolimab, Enzastaurin, Epirubicin, Erdafitinib, Etirinotecan Pegol, Everolimus, Exemestane, Favezelimab, Ferumoxytol, Fianlimab, Ficlatuzumab, Finasteride, Fludeoxyglucose, Fluorouracil, Fluzoparib, Fulvestrant, Gimeracil, Gimistotug, Heparin, Hydroxychloroquine, Ibrutinib, Imetelstat, Imiquimod, Iniparib, Inositol, Ipatasertib, Irinotecan, Itacitinib, Itraconazole, Ixabepilone, Izalontamab, Ladarixin, Lapatinib, Lenalidomide, Lifileucel, Linifanib, Linsitinib, Lurbinectedin, Metformin, Methotrexate, Methylprednisolone, Metronidazole, Mifepristone, Minocycline, Montelukast, Motexafin Gadolinium, Muparfostat, Naloxegol, Naquotinib, Nelfinavir, Neratinib, Niacinamide, Nimotuzumab, Nitroglycerin, Obinutuzumab, Olaratumab, Olmutinib, Ombrabulin, Oteracil, Padeliporfin, Palbociclib, Panitumumab, Patritumab Deruxtecan, Pazopanib, Pegilodecakin, Pemigatinib, Penpulimab, Pentoxifylline, Pertuzumab, Pevonedistat, Pioglitazone, Ponatinib, Pralatrexate, Prednisone, Pucotenlimab, Quavonlimab, Ranpirnase, Recombinant Human Thrombopoietin, Regramostim, Relatlimab, Ridaforolimus, Rocapuldencel-T, Rofecoxib, Romidepsin, Ruxolitinib, Sapacitabine, Saracatinib, Sargramostim, Sasanlimab, Sildenafil, Simvastatin, Sovatelitide, Spartalizumab, Suramin, Surufatinib, TECHNETIUM TC 99M SULFUR COLLOID, Tadalafil, Talazoparib, Tasisulam, Tegafur, Temsirolimus, Tepotinib, Teprotumumab, Thalidomide, Thymalfasin, Tifcemalimab, Tigatuzumab, Tipifarnib, Trabedersen, Trametinib, Transplatin, Trastuzumab, Trastuzumab Emtansine, Trastuzumab Vedotin, Treosulfan, Triapine, Trilaciclib, Tucidinostat, Tunlametinib, Uracil, Vatalanib, Vemurafenib, Vinflunine, Vintafolide, Vitespen, Volasertib, Volrustomig, Vorinostat, Vosaroxin, Zalutumumab, Zibotentan.

Drug target analysis

Approved (phase 4): 39 · Phase ≥3: 42 · Phased (≥1): 46 · Undrugged: 29

Druggability breadth: 69 of 100 evidence-associated genes (69%) 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
EGFR	LEVODOPA
BRAF	VEMURAFENIB
ERBB2	CLOTRIMAZOLE
KRAS	VEMURAFENIB
PIK3CA	IDELALISIB
ROS1	LORLATINIB
STK11	FEDRATINIB
AURKA	INAMRINONE
TP53	NITROFURANTOIN
TYMS	FOLIC ACID
WEE1	FEDRATINIB
CCND1	PALBOCICLIB
CD274	MOCLOBEMIDE
SLTM	CABOZANTINIB
KEAP1	DUTASTERIDE
CXCR4	PLERIXAFOR
DDR2	PONATINIB
ERBB3	MOBOCERTINIB
ERCC2	SUNITINIB
FGFR1	PONATINIB
ABCB1	PROGESTERONE
ALK	CERITINIB
IGF1R	FEDRATINIB
BIRC5	BENZIODARONE
JAK1	FEDRATINIB
KIT	PONATINIB
ARAF	VEMURAFENIB
MAPK1	PHENYLBUTAZONE
ABL1	PONATINIB
NFE2L2	DIMETHYL FUMARATE
NTRK1	PONATINIB
NTRK3	FEDRATINIB
PDGFRA	PONATINIB
PIM1	COLCHICINE
RET	PONATINIB
TERT	BERBERINE
CAMK2D	MOMELOTINIB
CASP8	PRIMAQUINE PHOSPHATE
CHRNA5	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAPK1	324	4
TP53	196	4
EGFR	175	4
RET	135	4
ABL1	122	4
ABCB1	119	4
KIT	99	4
FGFR1	93	4
ERBB2	83	4
PDGFRA	77	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	ABCB1, EGFR, ERBB2, MAPK1, TP53
ERLOTINIB HYDROCHLORIDE	4	EGFR, ERBB2
CISPLATIN	4	EGFR
PONATINIB	4	ABL1, BRAF, DDR2, EGFR, ERBB2, FGFR1
AFATINIB	4	ABL1, EGFR, ERBB2, ERBB3, RET
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR, ERBB2
VEMURAFENIB	4	ARAF, BRAF, EGFR, KRAS, RET
FEDRATINIB	4	ABL1, ALK, AURKA, BRAF, CAMK2D, DDR2
AXITINIB	4	ABL1, AURKA, DDR2, EGFR, FGFR1, KIT
SORAFENIB	4	ABL1, ARAF, AURKA, BRAF, DDR2, EGFR
DASATINIB ANHYDROUS	4	ABL1, BRAF, DDR2, EGFR, KIT, RET
NICLOSAMIDE	4	AURKA, EGFR, FGFR1, KIT, MAPK1, TP53
SELUMETINIB	4	EGFR
TERFENADINE	4	ABCB1, EGFR
ALECTINIB	4	ALK, EGFR, RET, ROS1
NERATINIB	4	ABL1, EGFR, ERBB2, ERBB3, WEE1
IBRUTINIB	4	ABL1, EGFR, ERBB2, RET
AFATINIB DIMALEATE	4	ABL1, EGFR, ERBB2
CABOZANTINIB	4	ABL1, AURKA, DDR2, EGFR, ERBB2, FGFR1
DACOMITINIB	4	EGFR, ERBB2
DACOMITINIB ANHYDROUS	4	EGFR, ERBB2
CERITINIB	4	ABCB1, ABL1, ALK, EGFR, IGF1R, JAK1
VANDETANIB	4	ABL1, ALK, DDR2, EGFR, ERBB2, ERBB3
TRIBROMSALAN	4	EGFR, ERBB2, MAPK1
BOSUTINIB	4	ABL1, ALK, DDR2, EGFR, ERBB2, ERBB3
BITHIONOL	4	EGFR, ERBB2, MAPK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 32.

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
ABL1	3,282	Binding:3254, ADMET:16, Functional:10, Toxicity:2
ABCB1	3,063	Binding:2135, Functional:746, ADMET:182
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
ALK	1,815	Binding:1801, Functional:13, ADMET:1
RET	1,586	Binding:1573, Functional:10, ADMET:3
JAK1	1,502	Binding:1428, Functional:49, ADMET:24, Toxicity:1
AURKA	1,500	Binding:1483, Functional:10, ADMET:7
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
MAPK1	1,369	Binding:1348, Functional:16, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
NTRK1	1,194	Binding:1182, ADMET:7, Functional:5
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
IGF1R	1,091	Binding:1037, Functional:53, ADMET:1
PIM1	1,008	Binding:971, Functional:30, ADMET:4, Toxicity:3
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
NFE2L2	861	Binding:812, Functional:49
CCND1	576	Binding:574, Functional:1, ADMET:1
CXCR4	560	Binding:386, Functional:174
KEAP1	537	Binding:535, Functional:1, ADMET:1
CD274	525	Binding:520, Functional:5
ROS1	461	Binding:459, Functional:2
NTRK3	408	Binding:400, Functional:4, ADMET:4
TERT	391	Binding:389, Functional:2
DDR2	389	Binding:386, ADMET:3
WEE1	385	Binding:374, Functional:7, ADMET:2, Unclassified:1, Toxicity:1
TYMS	376	Binding:373, ADMET:2, Functional:1
CAMK2D	338	Binding:337, Functional:1
STK11	244	Binding:244
SMARCA4	230	Binding:207, ADMET:12, Functional:11
ERBB3	169	Binding:169
CASP8	116	Binding:106, Functional:10
ARAF	92	Binding:92
PBK	90	Binding:89, Functional:1
RRM1	83	Binding:80, Functional:3
BIRC5	65	Binding:63, Functional:2
RB1	59	Binding:59
CBLB	58	Binding:58
BCL2L11	38	Binding:36, Functional:2
ABCC10	30	Functional:24, Binding:6
ERCC1	28	Binding:28
NOTCH1	23	Binding:19, ADMET:4
CHRNA5	21	Binding:16, Functional:4, ADMET:1
NRAS	18	Binding:18
SLTM	14	Binding:14
HAVCR2	13	Binding:13
POLD1	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EGFR	2.7.10.1	receptor protein-tyrosine kinase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
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
ROS1	2.7.10.1	receptor protein-tyrosine kinase
RRM1	1.17.4.1	ribonucleoside-diphosphate reductase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
AURKA	2.7.11.1	non-specific serine/threonine protein kinase
TYMS	2.1.1.45	thymidylate synthase
WEE1	2.7.10.2	non-specific protein-tyrosine kinase
DDR2	2.7.10.1	receptor protein-tyrosine kinase
ERBB3	2.7.10.1	receptor protein-tyrosine kinase
ERCC2	3.6.4.12	DNA helicase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
ABCB1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
ALK	2.7.10.1	receptor protein-tyrosine kinase
ABCC10	7.6.2.2	ABC-type xenobiotic transporter
IGF1R	2.7.10.1	receptor protein-tyrosine kinase
JAK1	2.7.10.2	non-specific protein-tyrosine kinase
KIT	2.7.10.1	receptor protein-tyrosine kinase
ARAF	2.7.10.2	non-specific protein-tyrosine kinase
MAPK1	2.7.11.24	mitogen-activated protein kinase
ABL1	2.7.10.2	non-specific protein-tyrosine kinase
NTRK1	2.7.10.1	receptor protein-tyrosine kinase
NTRK3	2.7.10.1	receptor protein-tyrosine kinase
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
PIM1	2.7.11.1	non-specific serine/threonine protein kinase
POLD1	2.7.7.7	DNA-directed DNA polymerase
RET	2.7.10.1	receptor protein-tyrosine kinase
CAMK2D	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
CASP8	3.4.22.61	caspase-8

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EGFR	6,531
BRAF	1,442
ERBB2	1,221
KRAS	861
PIK3CA	2,034
ROS1	461
SMARCA4	230
STK11	244
AURKA	1,500
TP53	869
TYMS	376
WEE1	385
CCND1	576
CD274	525
KEAP1	537
CXCR4	560
DDR2	389
ERBB3	169
FGFR1	1,465
ABCB1	3,063
ALK	1,815
IGF1R	1,091
JAK1	1,502
KIT	2,305
MAPK1	1,369
ABL1	3,282
NFE2L2	861
NTRK1	1,194
NTRK3	408
PDGFRA	1,172

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

25 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)
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	ABCB1, EGFR, ERBB2, MAPK1, TP53
ERLOTINIB HYDROCHLORIDE	4	EGFR, ERBB2
PONATINIB	4	ABL1, BRAF, DDR2, EGFR, ERBB2, FGFR1
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR, ERBB2
VEMURAFENIB	4	ARAF, BRAF, EGFR, KRAS, RET
FEDRATINIB	4	ABL1, ALK, AURKA, BRAF, CAMK2D, DDR2
AXITINIB	4	ABL1, AURKA, DDR2, EGFR, FGFR1, KIT
SORAFENIB	4	ABL1, ARAF, AURKA, BRAF, DDR2, EGFR
DASATINIB ANHYDROUS	4	ABL1, BRAF, DDR2, EGFR, KIT, RET
NICLOSAMIDE	4	AURKA, EGFR, FGFR1, KIT, MAPK1, TP53
SELUMETINIB	4	EGFR
TERFENADINE	4	ABCB1, EGFR
NERATINIB	4	ABL1, EGFR, ERBB2, ERBB3, WEE1
IBRUTINIB	4	ABL1, EGFR, ERBB2, RET
AFATINIB DIMALEATE	4	ABL1, EGFR, ERBB2
CABOZANTINIB	4	ABL1, AURKA, DDR2, EGFR, ERBB2, FGFR1
DACOMITINIB	4	EGFR, ERBB2
CERITINIB	4	ABCB1, ABL1, ALK, EGFR, IGF1R, JAK1
TRIBROMSALAN	4	EGFR, ERBB2, MAPK1
BOSUTINIB	4	ABL1, ALK, DDR2, EGFR, ERBB2, ERBB3
BITHIONOL	4	EGFR, ERBB2, MAPK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	39	EGFR, BRAF, ERBB2, KRAS, PIK3CA, ROS1, STK11, AURKA, TP53, TYMS (+29 more)
B	Phased (≥1) drug, not yet approved	7	NRAS, RRM1, SMARCA4, PBK, NOTCH1, RB1, BCL2L11
C	Druggable family + PDB, no drug	3	NRG1, HAVCR2, NALCN
D	Druggable family + AlphaFold only, no drug	5	ABCC10, ADGRF3, SCYL2, SLC17A8, SLC35D2
E	Difficult family or no structure, no drug	21	CDKN2A, ETS2, TSC1, XRCC1, CBLB, CUL3, ERCC1, GNAS, AREG, SMAD4 (+11 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ETS2	0	TP53
NRG1	0	EGFR, ERBB3
HAVCR2	13	CD274
CUL3	7	KEAP1
ERCC1	28	ERCC2
AREG	1	EGFR, ERBB3
NF1	0	KRAS, BRAF, NRAS
CDKN2A	2	—
TSC1	0	—
XRCC1	0	—
CBLB	58	—
GNAS	0	—
ABCC10	30	—
SMAD4	6	—
POLD1	8	—
RASA1	0	—
MYNN	2	—
APCDD1	0	—
TP63	0	—
SEPTIN7	1	—
CDH8	0	—
VTI1A	0	—
ADGRF3	2	—
NALCN	0	—
SCYL2	0	—
SLC17A8	0	—
SLC35D2	0	—
FOXP4	0	—
ANKS1A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5,061.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	505
PHASE2	381
PHASE4	78
PHASE1/PHASE2	70
PHASE2/PHASE3	66

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03340506	PHASE4	RECRUITING	Dabrafenib and/or Trametinib Rollover Study
NCT05144997	PHASE4	ACTIVE_NOT_RECRUITING	Lorlatinib Continuation Study
NCT05160922	PHASE4	ACTIVE_NOT_RECRUITING	Crizotinib Continuation Clinical Study
NCT05172739	PHASE4	RECRUITING	Opioid Free Anaesthesia-Analgesia Strategy on Surgical Stress and Immunomodulation in Elective VATS-Lobectomy for NSCLC
NCT05689671	PHASE4	ACTIVE_NOT_RECRUITING	Pemetrexed-free vs. Pemetrexed-based Immunochemotherapy in Metastatic TTF-1 Negative Lung Adenocarcinoma
NCT05748093	PHASE4	RECRUITING	Improving Osimertinib Exposure and Cost-effectiveness Using Pharmacokinetic Boosting With Cobicistat
NCT06330038	PHASE4	RECRUITING	Anesthesia and Non-small Cell Lung Cancer Recurrence
NCT06356675	PHASE4	NOT_YET_RECRUITING	A Single-arm Pilot Study of Tislelizumab Combined With Anlotinib in Patients With Advanced NSCLC With Driver-negative After Progression to Immunotherapy
NCT06483009	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Combination Therapy of Sintilimab and Chemotherapy With Cryoablation in NSCLC
NCT06646471	PHASE4	RECRUITING	PROspective Master-protocol for Evaluation of Systemic THErapeutics in Elderly With Thoracic Malignancies
NCT06893354	PHASE4	NOT_YET_RECRUITING	Explore the Mechanisms Underlying Disease Resistance and Potential Primary Resistance Mechanism of Induction Therapy Lorlatinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harboring ALK Positive Mutation Revealed by Single-cell RNA Sequencing and Spatial Transcriptomics
NCT06908070	PHASE4	RECRUITING	Chemoradiotherapy With Surgery Followed by Consolidation Durvalumab
NCT07092202	PHASE4	RECRUITING	Firmonertinib Combined With Intrathecal Injection for the Treatment of EGFR Mutant NSCLC With Leptomeningeal Metastases
NCT07279935	PHASE4	NOT_YET_RECRUITING	Osimertinib Combined With Chemotherapy in Patients Who Had Distant Recurrence After Adjuvant Osimertinib for EGFRm Resectable SIB-IIIA NSCLC.
NCT07320105	PHASE4	RECRUITING	Postoperative Radiotherapy for Postoperative N2 Metastases of NSCLC in the Immunotherapy Era (Phase II)
NCT07469488	PHASE4	NOT_YET_RECRUITING	A Clinical Trial on the Outcomes of Comprehensive Enhanced Prophylaxis Management (CEPM) in Chinese Patients With EGFR-Mutated Advanced NSCLC Receiving Amivantamab-Based Regimens
NCT00099541	PHASE4	COMPLETED	Non-small Cell Lung Cancer Registry
NCT00115206	PHASE4	COMPLETED	Neulasta® in Subjects With Advanced Non-Small-Cell Lung Cancer (NSCLC) During Chemotherapy
NCT00380718	PHASE4	COMPLETED	Chemotherapy for Patients With Non-Small Cell Lung Cancer
NCT00608868	PHASE4	COMPLETED	SELINE: Second-Line Iressa Phase IV Study in NSCLC Patients
NCT00686322	PHASE4	COMPLETED	Concurrent Chemoradiotherapy (CCRT) With Paclitaxel Plus Cisplatin in LA Non-small-cell Lung Cancer (NSCLC)
NCT00762346	PHASE4	COMPLETED	Efficacy and Safety Study of ZOMETA® in Treatment of High-level NTX Non Small Cell Lung Cancer With Bone Metastasis
NCT00765687	PHASE4	COMPLETED	Screening Non Small Cell Lung Cancer With Bone Metastasis and Efficacy and Safety Research of Receiving Bisphosphonates
NCT00770588	PHASE4	COMPLETED	Assess the Efficacy, Safety and Tolerability of Gefitinib (Iressa® 250mg) as Maintenance Therapy in Locally Advanced or Metastatic (Stage IIIB/IV) Non Small Cell Lung Cancer (NSCLC)
NCT00813332	PHASE4	UNKNOWN	Second-line Therapy Study of Combined Chemotherapy and Endostar to Patients With Non-Small Cell Lung Cancer(NSCLC)
NCT00883675	PHASE4	COMPLETED	Safety Study of Adjuvant Docetaxel-Carboplatin Treatment for Resected Lung Cancer
NCT00949910	PHASE4	COMPLETED	An Expanded Access Program of Tarceva (Erlotinib) in Participants With Advanced Non-Small Cell Lung Cancer (NSCLC)
NCT01000740	PHASE4	COMPLETED	A Study on the Long Term Survivals in an Expand Access Program (EAP) of Iressa
NCT01020786	PHASE4	COMPLETED	A Study in Non-squamous Non Small Cell Lung Cancer in Asian Patients
NCT01028729	PHASE4	UNKNOWN	A Study of Endostar Combined With Chemotherapy Followed by Endostar Maintenance Therapy to Treat Advanced Non-small Cell Lung Cancer (NSCLC)
NCT01196078	PHASE4	COMPLETED	A Study of Tarceva (Erlotinib) in Elderly Patients With Advanced Non-Small Cell Lung Cancer
NCT01211002	PHASE4	UNKNOWN	Study of Concurrent Chemo-radiotherapy Combined With Recombinant Human Endostatin for Local Advanced Non-small Cell Lung Cancer (NSCLC)
NCT01230710	PHASE4	COMPLETED	A Study of Tarceva (Erlotinib) in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer Following 4 Cycles of Platinum-based Chemotherapy Without Disease Progression
NCT01287754	PHASE4	COMPLETED	A Study of Tarceva (Erlotinib) in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer Who Present EGFR Mutations
NCT01320501	PHASE4	SUSPENDED	Experience of Erlotinib in Patients With Advanced Non-Small Cell Lung Cancer
NCT01336192	PHASE4	UNKNOWN	Maintenance Gemcitabine in the Chinese Advanced Lung Cancer
NCT01402089	PHASE4	COMPLETED	Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients
NCT01442909	PHASE4	COMPLETED	Pemetrexed Followed by Docetaxel or in Reverse Sequence
NCT01465243	PHASE4	COMPLETED	Dose Escalation Of Icotinib In Previously Treated Patients With Routine Dose
NCT01646450	PHASE4	UNKNOWN	First-line Treatment With Icotinib in Elder NSCLC EGFR Mutated Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PEMETREXED	4	112
ERLOTINIB	4	55
GEFITINIB	4	38
VINORELBINE	4	30
DOCETAXEL ANHYDROUS	4	29
GEMCITABINE	4	23
OSIMERTINIB	4	23
DURVALUMAB	4	21
PEMBROLIZUMAB	4	20
ATEZOLIZUMAB	4	16
NIVOLUMAB	4	16
CRIZOTINIB	4	12
TISLELIZUMAB	4	12
ZOLEDRONIC ACID ANHYDROUS	4	12
DACOMITINIB ANHYDROUS	4	11
IPILIMUMAB	4	11
CARBOPLATIN	4	10
SUNITINIB	4	9
CEMIPLIMAB	4	7
VANDETANIB	4	7
AFATINIB	4	5
ALECTINIB	4	5
CETUXIMAB	4	5
BEVACIZUMAB	4	4
CISPLATIN	4	4
LENVATINIB	4	4
PACLITAXEL	4	4
ADAGRASIB	4	3
ENSARTINIB	4	3
FLUDEOXYGLUCOSE F 18	4	3

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 601 predictive associations from 807 curated evidence items; also 35 prognostic, 6 oncogenic, 2 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
ALK Fusion	Alectinib	Sensitivity/Response	CIViC A	EID12012 +8
ALK Fusion	Crizotinib	Sensitivity/Response	CIViC A	EID1187 +6
EGFR L858R	Erlotinib	Sensitivity/Response	CIViC A	EID2994 +5
EGFR T790M	Osimertinib	Sensitivity/Response	CIViC A	EID1592 +4
KRAS G12C	Sotorasib	Sensitivity/Response	CIViC A	EID9431 +4
ROS1 Fusion	Crizotinib	Sensitivity/Response	CIViC A	EID1030 +4
ALK Fusion	Ceritinib	Sensitivity/Response	CIViC A	EID11190 +3
ALK Fusion	Lorlatinib	Sensitivity/Response	CIViC A	EID11191 +3
EGFR L858R	Afatinib	Sensitivity/Response	CIViC A	EID2997 +3
MET Exon 14 Skipping Mutation	Tepotinib	Sensitivity/Response	CIViC A	EID11766 +3
RET Fusion	Selpercatinib	Sensitivity/Response	CIViC A	EID11318 +3
ALK Fusion	Brigatinib	Sensitivity/Response	CIViC A	EID11121 +2
EGFR Exon 19 Deletion	Afatinib	Sensitivity/Response	CIViC A	EID2996 +2
MET Exon 14 Skipping Mutation	Capmatinib	Sensitivity/Response	CIViC A	EID8847 +2
EGFR Exon 19 Deletion	Erlotinib	Sensitivity/Response	CIViC A	EID2995 +1
EGFR L858R OR EGFR Exon 19 Deletion	Osimertinib	Sensitivity/Response	CIViC A	EID11219 +1
EGFR L858R OR EGFR Exon 19 Deletion	Dacomitinib	Sensitivity/Response	CIViC A	EID11239 +1
EGFR L858R OR EGFR Exon 19 Deletion	Gefitinib	Sensitivity/Response	CIViC A	EID11241 +1
ERBB2 Exon 20 Insertion	Trastuzumab Deruxtecan	Sensitivity/Response	CIViC A	EID11765 +1
ROS1 Fusion	Entrectinib	Sensitivity/Response	CIViC A	EID11123 +1
ALK Mutation	Lorlatinib	Sensitivity/Response	CIViC A	EID11286
BRAF V600E	Dabrafenib + Trametinib	Sensitivity/Response	CIViC A	EID3017
EGFR D770_N771insGT OR EGFR D770_N771insD OR EGFR D770_N771insF OR EGFR D770_N771insGD OR EGFR D770_N771insT OR EGFR N771delinsCH OR EGFR N771delinsGF OR EGFR N771delinsRD OR EGFR N771delinsSQRGH OR EGFR N771_P772insDN	Sunvozertinib	Sensitivity/Response	CIViC A	EID12632
EGFR D770delinsGY OR EGFR D770_N771insY OR EGFR N771_P772insT OR EGFR H773_V774insGNPH OR EGFR A767_S768insTLA OR EGFR S768_V769insLDS OR EGFR V769_D770insCV OR EGFR V769_D770insGA OR EGFR V769_D770insGVASV OR EGFR D770delinsAS	Sunvozertinib	Sensitivity/Response	CIViC A	EID12631
EGFR Exon 20 Insertion	Amivantamab	Sensitivity/Response	CIViC A	EID11227
EGFR Exon 20 Insertion	Mobocertinib	Sensitivity/Response	CIViC A	EID11228
EGFR Exon 20 Insertion	Chemotherapy + Amivantamab	Sensitivity/Response	CIViC A	EID12014
EGFR Exon 20 Insertion	Sunvozertinib	Sensitivity/Response	CIViC A	EID12718
EGFR G719	Afatinib	Sensitivity/Response	CIViC A	EID11242
EGFR H773_V774insH OR EGFR D770_N771insG OR EGFR H773_V774insNPH OR EGFR A763_Y764insFQEA OR EGFR V774_C775insHV OR EGFR H773_V774insPH OR EGFR H773_V774insAH OR EGFR D770_N771insH OR EGFR N771dup	Sunvozertinib	Sensitivity/Response	CIViC A	EID12630

+571 more predictive associations (showing top 30 by evidence level).