Colorectal carcinoma

Summary

Colorectal carcinoma (MONDO:0024331) is a cancer with 60 cohort genes (13 GWAS associations across 16 studies; 58 CIViC-evidence somatic drivers; 7 ClinVar predisposition records) and 4,934 clinical trials. The dominant Reactome pathway is Signaling by ERBB2 KD Mutants (10 cohort genes). Molecularly, MSI High confers sensitivity to Ipilimumab/Nivolumab Regimen in Colorectal Cancer (CIViC Level A); 411 further subtype–drug associations are mapped below. Top therapeutic interventions include bevacizumab, leucovorin, and irinotecan.

At a glance

• Classification: Cancer
• Cohort genes: 60
• GWAS associations: 13
• ClinVar variants: 7
• Clinical trials: 4,934
• Precision-medicine evidence (CIViC): 412 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	colorectal carcinoma
Mondo ID	MONDO:0024331
EFO	EFO:1001951
DOID	DOID:0080199
NCIT	C2955
UMLS	C0009402
MedGen	3170
Anatomy (UBERON)	UBERON:0012652
Is cancer (heuristic)	yes

Also known as: cancer of large bowel · cancer of large intestine · cancer of the large bowel · cancer of the large intestine · carcinoma of colorectum · carcinoma of large bowel · carcinoma of large intestine · carcinoma of the large bowel · carcinoma of the large intestine · colorectal (colon or rectal) cancer · colorectal cancer · colorectal carcinoma · colorectum carcinoma · CRC · large bowel cancer · large bowel carcinoma · large intestine cancer · large intestine carcinoma

Data availability: 7 ClinVar variants · 13 GWAS associations (16 studies) · 195 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › intestinal neoplasm › colorectal neoplasm › colorectal cancer › colorectal carcinoma

Related subtypes (4): rectal cancer, malignant colon neoplasm, familial colorectal cancer, colorectal lymphoma

Subtypes (4): colon carcinoma, colorectal adenocarcinoma, colorectal squamous cell carcinoma, rectal carcinoma

Genetics & variants

GWAS landscape

13 GWAS associations across 16 studies. Top hits map to 12 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6507874	1e-17	SMAD7	?	0.85
rs58658771	2e-16	SCG5 - GREM1	?	1.21
rs6983267	3e-16	PCAT1, CASC8, POU5F1B, CCAT2	?	0.86
rs10505477	3e-16	PCAT1, CASC8, POU5F1B	A	0.15
rs7130173	4e-12	POU2AF2	?	1.15
rs139427218	2e-11	SLC33A1	C	2.17
rs72746180	8e-11	LINC00604	?	1.14
rs1741640	4e-09	LAMA5	?	0.87
rs12135286	4e-09	LINC01705	?	1.14
rs16892766	7e-09	LINC00536 - EIF3H	?	1.21
rs74106363	3e-08	RPL6P25 - SLC6A15	?	0.81
rs2300985	1e-06	COX15, CUTC	?	0.89

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90432151	Jiang Y	2023	116,382	213,325	A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders.
GCST90297588	Auwerx C	2024	6,200	212,260	Rare copy-number variants as modulators of common disease susceptibility.
GCST90297642	Auwerx C	2024	6,200	212,260	Rare copy-number variants as modulators of common disease susceptibility.
GCST90297693	Auwerx C	2024	6,200	212,260	Rare copy-number variants as modulators of common disease susceptibility.
GCST90297735	Auwerx C	2024	6,200	212,260	Rare copy-number variants as modulators of common disease susceptibility.
GCST90475170	Verma A	2024	6,064	309,604	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90131430	Jordahl KM	2022	4,141	5,021	Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region.
GCST90476580	Verma A	2024	1,458	314,210	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476579	Verma A	2024	876	54,629	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479528	Verma A	2024	876	54,629	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	11
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	7
intergenic_variant	2
non_coding_transcript_exon_variant	2
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6507874	18	48922435	T>A,C	0.05	intron_variant	SMAD7	1e-17	Tier 4: intronic/intergenic
rs58658771	15	32709533	T>A,C,G	0.05	intergenic_variant	SCG5 - GREM1	2e-16	Tier 4: intronic/intergenic
rs6983267	8	127401060	G>T	0.05	non_coding_transcript_exon_variant	PCAT1, CASC8, POU5F1B, CCAT2	3e-16	Tier 4: intronic/intergenic
rs10505477	8	127395198	A>C,G,T	0.5	intron_variant	PCAT1, CASC8, POU5F1B	3e-16	Tier 4: intronic/intergenic
rs7130173	11	111283347	A>C,T	0.05	intron_variant	POU2AF2	4e-12	Tier 4: intronic/intergenic
rs139427218	3	155846287	C>T	0.001	intron_variant	SLC33A1	2e-11	Tier 4: intronic/intergenic
rs72746180	5	40240318	A>C	0.05	non_coding_transcript_exon_variant	LINC00604	8e-11	Tier 4: intronic/intergenic
rs1741640	20	62357358	T>A,C,G	0.05	intron_variant	LAMA5	4e-09	Tier 4: intronic/intergenic
rs12135286	1	222045419	C>T	0.05	intron_variant	LINC01705	4e-09	Tier 4: intronic/intergenic
rs16892766	8	116618444	A>C	0.05	regulatory_region_variant	LINC00536 - EIF3H	7e-09	Tier 3: regulatory
rs74106363	12	83270580	A>C,T	0.05	intergenic_variant	RPL6P25 - SLC6A15	3e-08	Tier 4: intronic/intergenic
rs2300985	10	99717148	G>A	0.05	intron_variant	COX15, CUTC	1e-06	Tier 4: intronic/intergenic

ClinVar germline variants

7 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
574856	NM_001429.4(EP300):c.4585C>T (p.Arg1529Ter)	EP300	Pathogenic	criteria provided, multiple submitters, no conflicts
947782	NM_001429.4(EP300):c.832del (p.Thr278fs)	EP300	Pathogenic	criteria provided, single submitter
617634	NM_005368.3(MB):c.292C>T (p.His98Tyr)	MB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
928703	NM_006231.4(POLE):c.1306C>T (p.Pro436Ser)	POLE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1327070	NM_004655.4(AXIN2):c.1060-2A>G	AXIN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1388960	NM_001429.4(EP300):c.7153C>T (p.Leu2385Phe)	EP300	Uncertain significance	criteria provided, single submitter
4278478	NM_000964.4(RARA):c.1071G>C (p.Glu357Asp)	RARA	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 180 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
POLE	Act	ACC,BLCA	CIViC #4386
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
ARID1A	LoF	BL,BLCA,BRCA,CCRCC,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,GBC,GBM,HCC,LGGNOS,LUAD,LUNG,LUSC,MBL,MLYM,MT,NHL,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PRAD,RCC,SCLC,SKIN,STAD,UCEC,UCS,UTUC	CIViC #6559
THBS2			CIViC #5761
TOP1	Act	BCC,HCC	CIViC #5845
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
TYMS			CIViC #5971
UGT1A			CIViC #6023
VEGFA			CIViC #6071
PPP1R15A			CIViC #9722
FBXW7	LoF	ANSC,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HNSC,LUAD,LUSC,MBL,NETNOS,NPC,PAAD,PAST,READ,STAD,UCEC,UCS	CIViC #12903
HSPH1			CIViC #8614
CDKN1A	LoF	BLCA,CHRCC,HCC	CIViC #913
CDX2	LoF	ESCA	CIViC #927
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52
SLFN11			CIViC #16872
DCC	LoF	COADREAD,ESCA,HCC,PAAD,PRAD	CIViC #1396
DKK1			CIViC #9171
SH2B3	Act	MDS	CIViC #7954
MIR218-1			CIViC #24938
EGFR	Act	BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC	CIViC #19
EIF4EBP1			CIViC #1655
EPAS1	Act	PGNG	CIViC #1705
EPHB4			CIViC #1721
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
ERBB3	Act	BLCA,BRCA,CESC,CHOL,COADREAD,NBL,PRAD,STAD,UCEC,UCS,UTUC	CIViC #1733
EREG			CIViC #1737
EZH2	Act	ALL,AML,DLBCLNOS,ES,MLYM,NHL	CIViC #63
FGFR1	Act	BLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTC	CIViC #1885
FLT3	Act	ALL,AML	CIViC #24

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POLE	Orphanet:352712	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome
POLE	Orphanet:440437	Familial colorectal cancer Type X
POLE	Orphanet:447877	Polymerase proofreading-related polyposis
POLE	Orphanet:85173	IMAGe syndrome
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
ARID1A	Orphanet:1465	Coffin-Siris syndrome
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
TYMS	Orphanet:1775	Dyskeratosis congenita
FBXW7	Orphanet:528084	Non-specific syndromic intellectual disability
DCC	Orphanet:238722	Familial congenital mirror movements
DCC	Orphanet:2744	Horizontal gaze palsy with progressive scoliosis
DCC	Orphanet:478	Kallmann syndrome
DKK1	Orphanet:268882	Arnold-Chiari malformation type I
DKK1	Orphanet:85193	Idiopathic juvenile osteoporosis
SH2B3	Orphanet:3318	Essential thrombocythemia
SH2B3	Orphanet:391366	Growth retardation-mild developmental delay-chronic hepatitis syndrome
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
EPAS1	Orphanet:247511	Autosomal dominant secondary polycythemia
EPAS1	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
EPAS1	Orphanet:324299	Multiple paragangliomas associated with polycythemia

Cohort genes → proteins

60 cohort genes, 58 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	55
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
POLE	HGNC:9177	ENSG00000177084	Q07864	DNA polymerase epsilon catalytic subunit A	clinvar,civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	civic_evidence
THBS2	HGNC:11786	ENSG00000186340	P35442	Thrombospondin-2	civic_evidence
TOP1	HGNC:11986	ENSG00000198900	P11387	DNA topoisomerase 1	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
TYMS	HGNC:12441	ENSG00000176890	P04818	Thymidylate synthase	civic_evidence
UGT1A	HGNC:12529			UDP glucuronosyltransferase family 1 member A complex locus	civic_evidence
VEGFA	HGNC:12680	ENSG00000112715	P15692	Vascular endothelial growth factor A, long form	civic_evidence
PPP1R15A	HGNC:14375	ENSG00000087074	O75807	Protein phosphatase 1 regulatory subunit 15A	civic_evidence
FBXW7	HGNC:16712	ENSG00000109670	Q969H0	F-box/WD repeat-containing protein 7	civic_evidence
HSPH1	HGNC:16969	ENSG00000120694	Q92598	Heat shock protein 105 kDa	civic_evidence
CDKN1A	HGNC:1784	ENSG00000124762	P38936	Cyclin-dependent kinase inhibitor 1	civic_evidence
CDX2	HGNC:1806	ENSG00000165556	Q99626	Homeobox protein CDX-2	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
SLFN11	HGNC:26633	ENSG00000172716	Q7Z7L1	Schlafen family member 11	civic_evidence
DCC	HGNC:2701	ENSG00000187323	P43146	Netrin receptor DCC	civic_evidence
DKK1	HGNC:2891	ENSG00000107984	O94907	Dickkopf-related protein 1	civic_evidence
SH2B3	HGNC:29605	ENSG00000111252	Q9UQQ2	SH2B adapter protein 3	civic_evidence
MIR218-1	HGNC:31595	ENSG00000207732		microRNA 218-1	civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
EIF4EBP1	HGNC:3288	ENSG00000187840	Q13541	Eukaryotic translation initiation factor 4E-binding protein 1	civic_evidence
EPAS1	HGNC:3374	ENSG00000116016	Q99814	Endothelial PAS domain-containing protein 1	civic_evidence
EPHB4	HGNC:3395	ENSG00000196411	P54760	Ephrin type-B receptor 4	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
ERBB3	HGNC:3431	ENSG00000065361	P21860	Receptor tyrosine-protein kinase erbB-3	civic_evidence
EREG	HGNC:3443	ENSG00000124882	O14944	Proepiregulin	civic_evidence
EZH2	HGNC:3527	ENSG00000106462	Q15910	Histone-lysine N-methyltransferase EZH2	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
FLT3	HGNC:3765	ENSG00000122025	P36888	Receptor-type tyrosine-protein kinase FLT3	civic_evidence
AKT1	HGNC:391	ENSG00000142208	P31749	RAC-alpha serine/threonine-protein kinase	civic_evidence
ALCAM	HGNC:400	ENSG00000170017	Q13740	CD166 antigen	civic_evidence
GNAS	HGNC:4392	ENSG00000087460	O95467	Neuroendocrine secretory protein 55	civic_evidence
GSTP1	HGNC:4638	ENSG00000084207	P09211	Glutathione S-transferase P	civic_evidence
HIF1A	HGNC:4910	ENSG00000100644	Q16665	Hypoxia-inducible factor 1-alpha	civic_evidence
HLA-C	HGNC:4933	ENSG00000204525	P10321	HLA class I histocompatibility antigen, C alpha chain	civic_evidence
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	civic_evidence
HSPA5	HGNC:5238	ENSG00000044574	P11021	Endoplasmic reticulum chaperone BiP	civic_evidence
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	civic_evidence
KDR	HGNC:6307	ENSG00000128052	P35968	Vascular endothelial growth factor receptor 2	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	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
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	civic_evidence
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	civic_evidence
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	civic_evidence
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	civic_evidence
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	civic_evidence
NRG1	HGNC:7997	ENSG00000157168	Q02297	Pro-neuregulin-1, membrane-bound isoform	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POLE	DNA polymerase epsilon catalytic subunit A	Catalytic component of the DNA polymerase epsilon complex.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
ARID1A	AT-rich interactive domain-containing protein 1A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
THBS2	Thrombospondin-2	Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions.
TOP1	DNA topoisomerase 1	Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
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…
VEGFA	Vascular endothelial growth factor A, long form	Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A.
PPP1R15A	Protein phosphatase 1 regulatory subunit 15A	Recruits the serine/threonine-protein phosphatase PPP1CA to prevents excessive phosphorylation of the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases an…
FBXW7	F-box/WD repeat-containing protein 7	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
HSPH1	Heat shock protein 105 kDa	Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release.
CDKN1A	Cyclin-dependent kinase inhibitor 1	Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest.
CDX2	Homeobox protein CDX-2	Transcription factor which regulates the transcription of multiple genes expressed in the intestinal epithelium.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
SLFN11	Schlafen family member 11	Inhibitor of DNA replication that promotes cell death in response to DNA damage.
DCC	Netrin receptor DCC	Receptor for netrin required for axon guidance.
DKK1	Dickkopf-related protein 1	Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6.
SH2B3	SH2B adapter protein 3	Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.
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.
EIF4EBP1	Eukaryotic translation initiation factor 4E-binding protein 1	Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation.
EPAS1	Endothelial PAS domain-containing protein 1	Transcription factor involved in the induction of oxygen regulated genes.
EPHB4	Ephrin type-B receptor 4	Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
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.
ERBB3	Receptor tyrosine-protein kinase erbB-3	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.
EREG	Proepiregulin	Ligand of the EGF receptor/EGFR and ERBB4.
EZH2	Histone-lysine N-methyltransferase EZH2	Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.
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.
FLT3	Receptor-type tyrosine-protein kinase FLT3	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells.
AKT1	RAC-alpha serine/threonine-protein kinase	AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
ALCAM	CD166 antigen	Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts.
GSTP1	Glutathione S-transferase P	Catalyzes conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
HIF1A	Hypoxia-inducible factor 1-alpha	Functions as a master transcriptional regulator of the adaptive response to hypoxia.
HLA-C	HLA class I histocompatibility antigen, C alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
HSPA5	Endoplasmic reticulum chaperone BiP	Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen.
APC	Adenomatous polyposis coli protein	Tumor suppressor.
KDR	Vascular endothelial growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
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.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).
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.
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.
NT5E	5’-nucleotidase	Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, with AMP being the preferred substrate.
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.
PIK3R1	Phosphatidylinositol 3-kinase regulatory subunit alpha	Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane.

Protein-family classification

Druggable: 26 · Difficult: 10 · Unknown: 24 · Druggable fraction: 0.43

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	12	5.5×	1e-05
Nuclear receptor	1	6.4×	0.321
Phosphatase	2	2.8×	0.321
Antibody/Immunoglobulin	4	1.9×	0.321
Enzyme (other)	7	1.4×	0.370
Transcription factor	7	1.0×	0.780
Scaffold/PPI	3	0.9×	0.780
Other/Unknown	24	0.7×	0.995

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POLE	Transcription factor	no	2.7.7.7	DNA-dir_DNA_pol_B_exonuc, DNA-dir_DNA_pol_B, RNaseH-like_sf
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
THBS2	Other/Unknown	no		EGF, TSP1_rpt, VWF_dom
TOP1	Enzyme (other)	yes	5.6.2.1	TopoI, TopoI_DNA-bd_euk, DNA_brk_join_enz
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
TYMS	Enzyme (other)	yes	2.1.1.45	Thymidylate_synthase, Thymidylate_synthase_AS, Thymidate_synth/dCMP_Mease_dom
UGT1A	Other/Unknown	no
VEGFA	Other/Unknown	no		PDGF/VEGF_dom, PD_growth_factor_CS, VEGF_C
PPP1R15A	Other/Unknown	no		Prot_Pase1_reg-su15A/B_C, PPP1R15
FBXW7	Scaffold/PPI	no		WD40_rpt, F-box_dom, WD40/YVTN_repeat-like_dom_sf
HSPH1	Other/Unknown	no		Hsp_70_fam, Heat_shock_70_CS, HSP70_peptide-bd_sf
CDKN1A	Other/Unknown	no		CDI_dom, CDKN1A, CDI_dom_sf
CDX2	Transcription factor	no		HTH_motif, HD, Caudal_activation_dom
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
SLFN11	Other/Unknown	no		Schlafen_AlbA_2_dom, SLFN_3-like_DNA/RNA_helicase, P-loop_NTPase
DCC	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
DKK1	Other/Unknown	no		Dickkopf_N, DKK1-4, Dkk1_Cys2
SH2B3	Scaffold/PPI	no		SH2, PH_domain, PH-like_dom_sf
MIR218-1	Other/Unknown	no
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
EIF4EBP1	Other/Unknown	no		EIF4EBP
EPAS1	Transcription factor	no		PAS, Nuc_translocat, PAC
EPHB4	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, 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
EREG	Other/Unknown	no		EGF
EZH2	Enzyme (other)	yes	2.1.1.356	SANT/Myb, SET_dom, EZH1/EZH2_N
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FLT3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
AKT1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
ALCAM	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
GNAS	Other/Unknown	no		NESP55, Gprotein_alpha_S, Gprotein_alpha_su
GSTP1	Enzyme (other)	yes	2.5.1.18	GST_pi, Glutathione_S-Trfase_N, GST_C
HIF1A	Transcription factor	no		PAS, HIF-1_alpha, PAC
HLA-C	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig_C1-set, Ig-like_dom
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
HSPA5	Other/Unknown	no		Hsp_70_fam, Heat_shock_70_CS, HSP70_peptide-bd_sf
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP
KDR	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
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
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
NRG1	Antibody/Immunoglobulin	yes		EGF, Neuregulin_C, Ig_sub2

Expression context

Cohort genes with no expression data: 1.

58 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)	59
unknown	1

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	11
ventricular zone	10
stromal cell of endometrium	6
ganglionic eminence	6
colonic epithelium	4
embryo	4
oocyte	4
secondary oocyte	4
lower esophagus mucosa	4
buccal mucosa cell	3
mucosa of stomach	3
monocyte	3
endometrium epithelium	3
adrenal tissue	3
right lung	3
type B pancreatic cell	3
cerebellar hemisphere	2
right testis	2
bone marrow cell	2
bronchial epithelial cell	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POLE	221	ubiquitous	marker	right hemisphere of cerebellum, right testis, cerebellar hemisphere
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
THBS2	272	ubiquitous	marker	pericardium, right coronary artery, stromal cell of endometrium
TOP1	278	ubiquitous	marker	oocyte, ventricular zone, secondary oocyte
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
TYMS	262	ubiquitous	marker	ventricular zone, embryo, trabecular bone tissue
UGT1A
VEGFA	297	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
PPP1R15A	283	ubiquitous	marker	mucosa of stomach, lower esophagus mucosa, omental fat pad
FBXW7	290	ubiquitous	marker	Brodmann (1909) area 23, calcaneal tendon, colonic epithelium
HSPH1	290	ubiquitous	marker	primordial germ cell in gonad, bronchial epithelial cell, epithelium of bronchus
CDKN1A	297	ubiquitous	marker	stromal cell of endometrium, mucosa of stomach, vena cava
CDX2	64	broad	marker	mucosa of transverse colon, rectum, transverse colon
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
SLFN11	215	ubiquitous	marker	monocyte, leukocyte, calcaneal tendon
DCC	154	broad	marker	cortical plate, right testis, left testis
DKK1	195	ubiquitous	marker	decidua, endometrium epithelium, stromal cell of endometrium
SH2B3	260	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
MIR218-1	66		yes	kidney, calcaneal tendon, adrenal tissue
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
EIF4EBP1	251	ubiquitous	marker	body of pancreas, parotid gland, lower esophagus mucosa
EPAS1	298	ubiquitous	marker	right lung, lower lobe of lung, adult organism
EPHB4	282	ubiquitous	marker	olfactory bulb, type B pancreatic cell, body of uterus
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
ERBB3	274	broad	marker	trigeminal ganglion, jejunal mucosa, dorsal root ganglion
EREG	174	broad	marker	buccal mucosa cell, amniotic fluid, upper leg skin
EZH2	216	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
FLT3	166	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 103.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
AKT1	16,601
KRAS	14,509
HSPA5	11,992
PTEN	11,626
EP300	10,122
HIF1A	9,734
ERBB2	9,659
EZH2	9,646

Intra-cohort edges

A	B	Sources
AKT1	EIF4EBP1	string_interaction
AKT1	HRAS	string_interaction
AKT1	PIK3CA	biogrid_interaction, string_interaction
AKT1	PIK3R1	string_interaction
AKT1	PTEN	string_interaction
ALCAM	EGFR	intact
ALCAM	NT5E	string_interaction
APC	AXIN2	string_interaction
APC	SLFN11	biogrid_interaction
ARAF	BRAF	biogrid_interaction, intact
ARAF	HRAS	intact
ARAF	KRAS	biogrid_interaction, intact
ARAF	NRAS	intact
AREG	EGFR	intact, string_interaction
AREG	ERBB2	string_interaction
AREG	ERBB3	string_interaction
AREG	EREG	string_interaction
ARID1A	MSH2	string_interaction
AXIN2	BARD1	intact
AXIN2	DKK1	string_interaction
AXIN2	SMAD4	intact
BARD1	SLFN11	string_interaction
BRAF	EGFR	biogrid_interaction
BRAF	FBXW7	biogrid_interaction
BRAF	HRAS	intact, string_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MLH1	string_interaction
BRAF	NRAS	biogrid_interaction, intact, string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	POLE	intact
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	TP53	string_interaction
CDKN1A	TP53	string_interaction
CDX2	EP300	biogrid_interaction
CDX2	FBXW7	biogrid_interaction
DCC	FLT3	biogrid_interaction
EGFR	EPHB4	intact
EGFR	ERBB2	intact, string_interaction
EGFR	ERBB3	biogrid_interaction, intact, string_interaction
EGFR	EREG	biogrid_interaction, intact, string_interaction
EGFR	HRAS	string_interaction
EGFR	HSPH1	intact
EGFR	NRAS	string_interaction
EGFR	NRG1	intact
EGFR	PIK3CA	string_interaction
EGFR	PIK3R1	string_interaction
EGFR	PTEN	string_interaction
EGFR	SH2B3	intact
EP300	EPAS1	biogrid_interaction, string_interaction
EP300	HIF1A	biogrid_interaction, intact, string_interaction

Structural data

PDB: 56 · AlphaFold-only: 2 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
GNAS	O95467	490
EGFR	P00533	388
TP53	P04637	313
HRAS	P01112	246
PIK3CA	P42336	135
BRAF	P15056	131
PIK3R1	P27986	105
FGFR1	P11362	83
GSTP1	P09211	68
ERBB2	P04626	63
TYMS	P04818	61
EP300	Q09472	60
VEGFA	P15692	56
KDR	P35968	54
NT5E	P21589	51
EPAS1	Q99814	43
AKT1	P31749	43
EZH2	Q15910	38
NRAS	P01111	35
HSPA5	P11021	33
APC	P25054	31
MSH2	P43246	30
NOTCH1	P46531	29
HIF1A	Q16665	25
EIF4EBP1	Q13541	24
EPHB4	P54760	23
ERBB3	P21860	23
POLE	Q07864	18
TOP1	P11387	15

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SH2B3	Q9UQQ2	63.45
SLTM	Q9NWH9	52.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 683. Enrichment computed across 60 evidence-associated genes (55 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 55 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by ERBB2 KD Mutants	10	76.9×	2e-14	EGFR, ERBB2, ERBB3, EREG, HRAS, KRAS, NRAS, NRG1 (+2 more)
RAF/MAP kinase cascade	15	16.7×	2e-12	BRAF, EGFR, ERBB2, ERBB3, EREG, FGFR1, FLT3, HRAS (+7 more)
SHC1 events in ERBB2 signaling	8	69.2×	2e-11	EGFR, ERBB2, ERBB3, EREG, HRAS, KRAS, NRAS, NRG1
Signaling by ERBB2 TMD/JMD mutants	8	69.2×	2e-11	EGFR, ERBB2, ERBB3, EREG, HRAS, KRAS, NRAS, NRG1
Signaling by FLT3 ITD and TKD mutants	7	96.9×	3e-11	CDKN1A, FLT3, HRAS, KRAS, NRAS, PIK3CA, PIK3R1
PI3K events in ERBB2 signaling	7	85.5×	7e-11	EGFR, ERBB2, ERBB3, EREG, NRG1, PIK3CA, PIK3R1
Signaling by ERBB2 ECD mutants	7	85.5×	7e-11	EGFR, ERBB2, HRAS, KRAS, NRAS, PIK3CA, PIK3R1
GRB2 events in ERBB2 signaling	7	80.8×	1e-10	EGFR, ERBB2, EREG, HRAS, KRAS, NRAS, NRG1
FLT3 Signaling	8	50.3×	2e-10	SH2B3, FLT3, AKT1, HRAS, KRAS, NRAS, PIK3CA, PIK3R1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	11	19.4×	5e-10	EGFR, ERBB2, ERBB3, EREG, FGFR1, FLT3, AKT1, AREG (+3 more)
Constitutive Signaling by Aberrant PI3K in Cancer	10	23.1×	8e-10	EGFR, ERBB2, ERBB3, EREG, FGFR1, FLT3, AREG, NRG1 (+2 more)
PIP3 activates AKT signaling	12	14.6×	1e-09	CDKN1A, EGFR, ERBB2, ERBB3, EREG, FGFR1, FLT3, AKT1 (+4 more)
GRB2 events in EGFR signaling	6	83.0×	2e-09	EGFR, EREG, HRAS, KRAS, AREG, NRAS
SHC1 events in EGFR signaling	6	77.9×	3e-09	EGFR, EREG, HRAS, KRAS, AREG, NRAS
Constitutive Signaling by EGFRvIII	6	77.9×	3e-09	EGFR, HRAS, KRAS, NRAS, PIK3CA, PIK3R1
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	6	62.3×	1e-08	EGFR, HRAS, KRAS, NRAS, PIK3CA, PIK3R1
Signaling by FLT3 fusion proteins	6	62.3×	1e-08	CDKN1A, HRAS, KRAS, NRAS, PIK3CA, PIK3R1
Signaling by FGFR4 in disease	5	86.5×	6e-08	HRAS, KRAS, NRAS, PIK3CA, PIK3R1
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	5	79.9×	9e-08	HRAS, KRAS, NRAS, PIK3CA, PIK3R1
Signaling by PDGFRA extracellular domain mutants	5	79.9×	9e-08	HRAS, KRAS, NRAS, PIK3CA, PIK3R1
ERBB2 Activates PTK6 Signaling	5	74.2×	1e-07	EGFR, ERBB2, ERBB3, EREG, NRG1
Downregulation of ERBB2 signaling	6	41.5×	2e-07	EGFR, ERBB2, ERBB3, EREG, AKT1, NRG1
SHC1 events in ERBB4 signaling	5	64.9×	3e-07	EREG, HRAS, KRAS, NRAS, NRG1
ERBB2 Regulates Cell Motility	5	64.9×	3e-07	EGFR, ERBB2, ERBB3, EREG, NRG1
Signaling by ERBB2	6	37.8×	3e-07	EGFR, ERBB2, ERBB3, EREG, AKT1, NRG1
GAB1 signalosome	5	57.7×	5e-07	EGFR, EREG, AREG, PIK3CA, PIK3R1
Tie2 Signaling	5	54.6×	6e-07	HRAS, KRAS, NRAS, PIK3CA, PIK3R1
Signaling by FGFR1 in disease	6	31.9×	7e-07	FGFR1, HRAS, KRAS, NRAS, PIK3CA, PIK3R1
VEGFR2 mediated cell proliferation	5	51.9×	7e-07	VEGFA, HRAS, KDR, KRAS, NRAS
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	47.2×	1e-06	HRAS, KRAS, NRAS, PIK3CA, PIK3R1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 58 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
epidermal growth factor receptor signaling pathway	8	34.2×	1e-07	BRAF, EGFR, ERBB2, ERBB3, EREG, AKT1, AREG, PIK3CA
negative regulation of apoptotic process	14	8.4×	5e-07	BRAF, TP53, VEGFA, DKK1, EGFR, ERBB2, ERBB3, AKT1 (+6 more)
positive regulation of cell population proliferation	14	8.1×	5e-07	VEGFA, CDX2, EGFR, EREG, EZH2, FGFR1, FLT3, HRAS (+6 more)
phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	25.4×	3e-06	EGFR, ERBB2, ERBB3, AKT1, PIK3CA, PIK3R1, PTEN
ERBB2-EGFR signaling pathway	4	116.2×	7e-06	EGFR, ERBB2, EREG, AREG
positive regulation of epithelial cell proliferation	6	25.3×	3e-05	VEGFA, EGFR, ERBB2, ERBB3, HRAS, NOTCH1
regulation of hematopoietic progenitor cell differentiation	3	174.3×	5e-05	VEGFA, KDR, RARA
positive regulation of blood vessel endothelial cell migration	5	33.8×	5e-05	VEGFA, FGFR1, AKT1, HIF1A, KDR
positive regulation of ERK1 and ERK2 cascade	8	11.7×	5e-05	BRAF, VEGFA, FBXW7, EGFR, HRAS, KDR, NOTCH1, NRG1
positive regulation of cell migration	9	9.6×	5e-05	VEGFA, EGFR, EZH2, AKT1, HRAS, HSPA5, APC, KDR (+1 more)
negative regulation of G1/S transition of mitotic cell cycle	5	30.9×	6e-05	CDKN1A, SLFN11, EZH2, APC, PTEN
positive regulation of MAPK cascade	8	11.1×	6e-05	VEGFA, EGFR, ERBB2, ERBB3, FGFR1, FLT3, HRAS, KDR
ERBB2-ERBB4 signaling pathway	3	145.3×	7e-05	ERBB2, EREG, NRG1
endocardial cell differentiation	3	145.3×	7e-05	SMAD4, NOTCH1, NRG1
positive regulation of peptidyl-serine phosphorylation	4	52.8×	7e-05	BRAF, EGFR, AKT1, ARAF
negative regulation of neuron apoptotic process	7	13.4×	7e-05	BRAF, ERBB3, HRAS, KDR, KRAS, MSH2, PIK3CA
negative regulation of cell population proliferation	10	7.3×	7e-05	TP53, CDKN1A, SH2B3, EREG, HRAS, APC, SMAD4, NOTCH1 (+2 more)
positive regulation of MAP kinase activity	4	44.7×	1e-04	ERBB2, EZH2, FGFR1, FLT3
negative regulation of gene expression	8	9.5×	1e-04	VEGFA, FBXW7, CDKN1A, HIF1A, HRAS, KDR, NOTCH1, PIK3CA
MAPK cascade	6	15.8×	1e-04	BRAF, FGFR1, HRAS, KRAS, ARAF, NRAS
positive regulation of gene expression	10	6.7×	1e-04	BRAF, TP53, VEGFA, DKK1, ERBB3, AKT1, HIF1A, KRAS (+2 more)
cellular response to vascular endothelial growth factor stimulus	4	38.7×	2e-04	VEGFA, AKT1, KDR, NOTCH1
angiogenesis	8	8.6×	2e-04	VEGFA, EPAS1, EPHB4, EREG, FGFR1, HIF1A, KDR, PIK3CA
ERBB2-ERBB3 signaling pathway	3	87.2×	2e-04	ERBB2, ERBB3, NRG1
positive regulation of transcription by RNA polymerase II	15	3.9×	2e-04	TP53, VEGFA, CDX2, EGFR, EP300, EPAS1, AKT1, HIF1A (+7 more)
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	4	34.2×	3e-04	TP53, CDKN1A, EP300, MSH2
positive regulation of endothelial cell proliferation	5	19.9×	3e-04	VEGFA, AKT1, HIF1A, KDR, NRAS
wound healing	5	19.6×	3e-04	CDKN1A, ERBB2, ERBB3, EREG, NRG1
epithelial cell maturation	3	79.2×	3e-04	VEGFA, EPAS1, KDR
insulin receptor signaling pathway	5	19.1×	3e-04	AKT1, HRAS, APC, PIK3CA, PIK3R1

Therapeutics

Drugs indicated for this disease

10 approved, 17 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bevacizumab	Approved (phase 4)
Capecitabine	Approved (phase 4)
Cetuximab	Approved (phase 4)
Ipilimumab	Approved (phase 4)
Levoleucovorin	Approved (phase 4)
Nivolumab	Approved (phase 4)
Panitumumab	Approved (phase 4)
Regorafenib	Approved (phase 4)
Trifluridine	Approved (phase 4)
Tucatinib	Approved (phase 4)
Atezolizumab	Phase 3 (in late-stage trials)
Calcium	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Cobimetinib	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Napabucasin	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
POLYETHYLENE GLYCOL 3350	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Raltitrexed	Phase 3 (in late-stage trials)
Ramucirumab	Phase 3 (in late-stage trials)
Relatlimab	Phase 3 (in late-stage trials)
Sintilimab	Phase 3 (in late-stage trials)
Thalidomide	Phase 3 (in late-stage trials)
Thymalfasin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Avelumab, Axitinib, Binimetinib, Cadonilimab, Clobetasol Propionate, Daratumumab, Dostarlimab, Durvalumab, Linaclotide, Oleclumab, Pemigatinib, Pexastimogene Devacirepvec, Regramostim, Ruxolitinib, Sargramostim, Serplulimab, Sunitinib, Tislelizumab, Toripalimab, Trametinib, Tucidinostat, Tunlametinib, Vemurafenib.

Drug target analysis

Approved (phase 4): 27 · Phase ≥3: 29 · Phased (≥1): 32 · Undrugged: 28

Druggability breadth: 50 of 60 evidence-associated genes (83%) 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
BRAF	VEMURAFENIB
TOP1	TOPOTECAN HYDROCHLORIDE
TP53	NITROFURANTOIN
TYMS	FOLIC ACID
VEGFA	VADADUSTAT
SLTM	CABOZANTINIB
EGFR	LEVODOPA
EPAS1	BELZUTIFAN
EPHB4	PONATINIB
ERBB2	CLOTRIMAZOLE
ERBB3	MOBOCERTINIB
EZH2	TAZEMETOSTAT
FGFR1	PONATINIB
FLT3	PONATINIB
AKT1	CAPIVASERTIB
GSTP1	ETHACRYNIC ACID
HIF1A	EMETINE
HRAS	LONAFARNIB
HSPA5	HEXACHLOROPHENE
KDR	VANDETANIB
KRAS	VEMURAFENIB
ARAF	VEMURAFENIB
PIK3CA	IDELALISIB
PIK3R1	IDELALISIB
PTP4A3	PENTAMIDINE
MB	ACETAMINOPHEN
RARA	BEXAROTENE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HIF1A	255	4
TP53	196	4
EGFR	175	4
KDR	172	4
FLT3	143	4
FGFR1	93	4
ERBB2	83	4
PIK3CA	67	4
BRAF	48	4
EPHB4	46	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	ARAF, BRAF, EGFR, KDR, KRAS
PONATINIB	4	BRAF, EGFR, EPHB4, ERBB2, FGFR1, FLT3
FEDRATINIB	4	BRAF, EGFR, EPHB4, FGFR1, FLT3, KDR
SORAFENIB	4	ARAF, BRAF, EGFR, EPHB4, ERBB2, FGFR1
DASATINIB ANHYDROUS	4	BRAF, EGFR, EPHB4
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, FGFR1, FLT3, KDR
INFIGRATINIB	4	BRAF, FGFR1, FLT3, KDR
REGORAFENIB	4	BRAF, FGFR1, FLT3, KDR
DABRAFENIB	4	ARAF, BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, EPHB4, FLT3
ABEMACICLIB	4	BRAF, EGFR, FLT3, KDR
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF, EPHB4
PAZOPANIB	4	BRAF, FGFR1, FLT3, KDR
DASATINIB	4	BRAF, EGFR, EPHB4, ERBB2, ERBB3, FGFR1
ERLOTINIB	4	BRAF, EGFR, EPHB4, ERBB2, ERBB3, FLT3
GEFITINIB	4	BRAF, EGFR, EPHB4, ERBB2, ERBB3, FLT3
IMATINIB	4	BRAF, EGFR, ERBB2, FLT3, KDR
TOPOTECAN HYDROCHLORIDE	4	HIF1A, TOP1
RIBAVIRIN	4	TOP1
AMSACRINE	4	HIF1A, TOP1, TP53
DOXORUBICIN	4	EPAS1, ERBB2, HIF1A, TOP1
TOPOTECAN	4	EPAS1, HIF1A, TOP1
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	HIF1A, TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 23.

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
FLT3	3,132	Binding:3096, Functional:24, ADMET:8, Toxicity:4
KDR	2,687	Binding:2594, Functional:64, ADMET:27, Toxicity:2
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
AKT1	1,942	Binding:1900, Functional:34, ADMET:7, Toxicity:1
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
TOP1	1,200	Binding:1161, Functional:38, ADMET:1
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
EZH2	839	Binding:833, Functional:6
EP300	767	Binding:763, Functional:3, ADMET:1
PIK3R1	493	Binding:470, ADMET:23
EPHB4	437	Binding:437
HIF1A	427	Binding:411, Functional:16
TYMS	376	Binding:373, ADMET:2, Functional:1
RARA	368	Binding:279, Functional:85, ADMET:4
EPAS1	241	Binding:233, Functional:8
NT5E	181	Binding:181
ERBB3	169	Binding:169
GSTP1	126	Binding:107, ADMET:19
ARAF	92	Binding:92
VEGFA	64	Binding:64
PTP4A3	58	Binding:58
HRAS	48	Binding:45, Functional:3
HSPA5	38	Binding:36, Functional:2
EIF4EBP1	33	Binding:33
APC	24	Binding:24
NOTCH1	23	Binding:19, ADMET:4
HSPH1	18	Binding:14, Functional:4
NRAS	18	Binding:18
CDKN1A	16	Binding:8, Functional:8
SLTM	14	Binding:14
AXIN2	14	Binding:14
MSH6	10	Binding:10
MSH2	9	Binding:9
PTEN	8	Binding:8
ARID1A	6	Binding:6
SLFN11	6	Binding:6
SMAD4	6	Binding:6
DKK1	5	Binding:5
PPP1R15A	1	Binding:1
HLA-C	1	Binding:1
AREG	1	Functional:1
MB	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POLE	2.7.7.7	DNA-directed DNA polymerase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
TOP1	5.6.2.1, 5.99.1.2	DNA topoisomerase, DNA topoisomerase
TYMS	2.1.1.45	thymidylate synthase
EGFR	2.7.10.1	receptor protein-tyrosine kinase
EPHB4	2.7.10.1	receptor protein-tyrosine kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
ERBB3	2.7.10.1	receptor protein-tyrosine kinase
EZH2	2.1.1.356	[histone H3]-lysine27 N-trimethyltransferase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
FLT3	2.7.10.1	receptor protein-tyrosine kinase
AKT1	2.7.11.1	non-specific serine/threonine protein kinase
GSTP1	2.5.1.18	glutathione transferase
HRAS	3.6.5.2	small monomeric GTPase
KDR	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
ARAF	2.7.10.2	non-specific protein-tyrosine kinase
NT5E	3.1.3.5	5’-nucleotidase
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
PIK3R1	2.7.1.153	phosphatidylinositol-4,5-bisphosphate 3-kinase
BARD1	2.3.2.27	RING-type E3 ubiquitin transferase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
EP300	2.3.1.48	histone acetyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRAF	1,442
TOP1	1,200
TP53	869
TYMS	376
EGFR	6,531
EPAS1	241
EPHB4	437
ERBB2	1,221
ERBB3	169
EZH2	839
FGFR1	1,465
FLT3	3,132
AKT1	1,942
GSTP1	126
HIF1A	427
KDR	2,687
KRAS	861
NT5E	181
PIK3CA	2,034
PIK3R1	493
EP300	767
RARA	368

Pharmacogenomics

Cohort genes with a PharmGKB record: 60; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

27 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)
VEMURAFENIB	4	ARAF, BRAF, EGFR, KDR, KRAS
PONATINIB	4	BRAF, EGFR, EPHB4, ERBB2, FGFR1, FLT3
FEDRATINIB	4	BRAF, EGFR, EPHB4, FGFR1, FLT3, KDR
SORAFENIB	4	ARAF, BRAF, EGFR, EPHB4, ERBB2, FGFR1
DASATINIB ANHYDROUS	4	BRAF, EGFR, EPHB4
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, FGFR1, FLT3, KDR
INFIGRATINIB	4	BRAF, FGFR1, FLT3, KDR
DABRAFENIB	4	ARAF, BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, EPHB4, FLT3
ABEMACICLIB	4	BRAF, EGFR, FLT3, KDR
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF, EPHB4
PAZOPANIB	4	BRAF, FGFR1, FLT3, KDR
DASATINIB	4	BRAF, EGFR, EPHB4, ERBB2, ERBB3, FGFR1
IMATINIB	4	BRAF, EGFR, ERBB2, FLT3, KDR
TOPOTECAN HYDROCHLORIDE	4	HIF1A, TOP1
RIBAVIRIN	4	TOP1
AMSACRINE	4	HIF1A, TOP1, TP53
DOXORUBICIN	4	EPAS1, ERBB2, HIF1A, TOP1
TOPOTECAN	4	EPAS1, HIF1A, TOP1
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	HIF1A, TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	27	BRAF, TOP1, TP53, TYMS, VEGFA, SLTM, EGFR, EPAS1, EPHB4, ERBB2 (+17 more)
B	Phased (≥1) drug, not yet approved	5	MSH6, NOTCH1, NRAS, NT5E, EP300
C	Druggable family + PDB, no drug	5	DCC, ALCAM, HLA-C, NRG1, PTEN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	23	POLE, ARID1A, THBS2, UGT1A, PPP1R15A, FBXW7, HSPH1, CDKN1A, CDX2, SLFN11 (+13 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
POLE	0	MSH6
EREG	0	EGFR, ERBB3
ALCAM	0	NT5E
AREG	1	EGFR, ERBB3
MLH1	0	MSH6
NRG1	0	EGFR, ERBB3
PTEN	8	TP53, AKT1
ARID1A	6	—
THBS2	0	—
UGT1A	0	—
PPP1R15A	1	—
FBXW7	0	—
HSPH1	18	—
CDKN1A	16	—
CDX2	0	—
SLFN11	6	—
DCC	0	—
DKK1	5	—
SH2B3	0	—
MIR218-1	0	—
EIF4EBP1	33	—
GNAS	0	—
HLA-C	1	—
APC	24	—
SMAD4	6	—
MSH2	9	—
BARD1	0	—
AXIN2	14	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4,934.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	485
PHASE3	370
PHASE1/PHASE2	111
PHASE4	77
PHASE2/PHASE3	57

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04281667	PHASE4	ACTIVE_NOT_RECRUITING	Mechanical Bowel Preparation and Oral Antibiotics Versus Mechanical Bowel Preparation Only Prior Rectal Surgery
NCT05726136	PHASE4	RECRUITING	Fluid Challenge and Plasma Volume, During Surgery
NCT05894694	PHASE4	RECRUITING	Survival Benefit of Compound Kushen Injection in the Treatment of Advanced Colorectal Cancer
NCT06090994	PHASE4	RECRUITING	Prevention of Recurrence and Metastasis of Colorectal Cancer by Comparing Huaier With Capecitabine Monotherapy
NCT06118762	PHASE4	RECRUITING	Clinical Study of Fruquintinib Combined With Raltitrexed in the Treatment of Metastatic Colorectal Cancer
NCT06550453	PHASE4	RECRUITING	Safety and Efficacy of Pembrolizumab in Combination with Bevacizumab + CapeOX in the Neoadjuvant Treatment of RAS-mutated, BRAF Wild-type, Microsatellite-stabilized, Locally Advanced Colorectal Cancer
NCT06562543	PHASE4	RECRUITING	A Trial to Evaluate the Safety and Activity of Fruquintinib in Minority Populations With Advanced, Previously Treated Colorectal Cancer
NCT06665334	PHASE4	NOT_YET_RECRUITING	To Explore the Effect of Huaier Granule on the Negative Conversion Rate After the CEA Level Increases Again After Colorectal Cancer Surgery
NCT06881563	PHASE4	NOT_YET_RECRUITING	Intrathecal Morphine Versus Epidural Analgesia for Laparoscopic Colon Surgery
NCT06935708	PHASE4	RECRUITING	Intrathecal Morphine Versus Epidural Analgesia for Open Colon Surgery
NCT07020468	PHASE4	ACTIVE_NOT_RECRUITING	Neoadjuvant Therapy （NALIRIFOX） for Locally Advanced Colon and Upper Rectal Cancer
NCT07094893	PHASE4	NOT_YET_RECRUITING	Anti-EGFR Agents in Patients With Right-sided Advanced Colorectal Cancer With Wild-type RAS and AREG/EREG High Status
NCT07152886	PHASE4	NOT_YET_RECRUITING	The Effects of Clostridium Butyricum on Adverse Events During Adjuvant Chemotherapy for Colorectal Cancer
NCT07446465	PHASE4	NOT_YET_RECRUITING	FOLFOX Chemotherapy Combined With Fruquintinib and Serplulimab as First-Line Conversion Therapy for Initially Unresectable pMMR/MSS Colorectal Cancer
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01175317	PHASE4	COMPLETED	Improvement of Fluid Balance in Patients Undergoing Surgery of the Colon and Rectum

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BEVACIZUMAB	4	177
LEUCOVORIN	4	153
IRINOTECAN	4	149
OXALIPLATIN	4	54
PANITUMUMAB	4	47
CETUXIMAB	4	37
CAPECITABINE	4	34
FLUOROURACIL	4	27
FLOXURIDINE	4	15
REGORAFENIB	4	12
FRUQUINTINIB	4	9
MITOMYCIN	4	8
ERLOTINIB	4	5
GEFITINIB	4	5
OCTREOTIDE ACETATE	4	5
LEVAMISOLE HYDROCHLORIDE	4	4
MELPHALAN	4	4
RALTITREXED	4	4
TEGAFUR	4	4
CALCIUM CARBONATE	4	2
CALCIUM GLUCONATE	4	2
CELECOXIB	4	2
DALTEPARIN SODIUM	4	2
FOLIC ACID	4	2
LEVOLEUCOVORIN CALCIUM	4	2
MAGNESIUM SULFATE	4	2
PENTOXIFYLLINE	4	2
PYRIDOXINE HYDROCHLORIDE	4	2
SUNITINIB	4	2
ALBUMIN HUMAN	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 412 predictive associations from 548 curated evidence items; also 58 prognostic, 42 oncogenic, 4 diagnostic, 2 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
MSI High	Ipilimumab/Nivolumab Regimen	Sensitivity/Response	CIViC A	EID12561 +1
BRAF V600E	Cetuximab + Encorafenib	Sensitivity/Response	CIViC A	EID9851
ERBB2 Overexpression	Trastuzumab + Tucatinib	Sensitivity/Response	CIViC A	EID11444
KRAS G12C	Cetuximab + Adagrasib	Sensitivity/Response	CIViC A	EID12063
KRAS G12C	Sotorasib + Panitumumab	Sensitivity/Response	CIViC A	EID12264
KRAS Wildtype	Cetuximab + Chemotherapy	Sensitivity/Response	CIViC A	EID11262
KRAS Wildtype	Chemotherapy + Panitumumab	Sensitivity/Response	CIViC A	EID11264
NRAS Wildtype	Chemotherapy + Panitumumab	Sensitivity/Response	CIViC A	EID11270
KRAS Exon 2 Mutation	Cetuximab	Resistance	CIViC A	EID993 +1
KRAS Mutation	Cetuximab + Panitumumab	Resistance	CIViC A	EID5345
NRAS Mutation	Panitumumab + Cetuximab	Resistance	CIViC A	EID5344
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC B	EID1405 +4
ERBB2 Amplification	Pertuzumab + Trastuzumab	Sensitivity/Response	CIViC B	EID11668 +2
BRAF V600E	Panitumumab + Vemurafenib	Sensitivity/Response	CIViC B	EID1413 +1
BRAF V600E	Vemurafenib + Irinotecan + Cetuximab	Sensitivity/Response	CIViC B	EID1902 +1
EGFR Expression	Cetuximab	Sensitivity/Response	CIViC B	EID1572 +1
KRAS G13D	Cetuximab	Sensitivity/Response	CIViC B	EID306 +1
NRAS Q61K	Dactolisib	Sensitivity/Response	CIViC B	EID2194 +1
AREG Expression	Panitumumab	Sensitivity/Response	CIViC B	EID1020
AREG Expression	Cetuximab	Sensitivity/Response	CIViC B	EID788
BRAF Class 2 Mutations	Cetuximab + Panitumumab	Sensitivity/Response	CIViC B	EID7574
BRAF Class 3 Mutations	Cetuximab + Panitumumab	Sensitivity/Response	CIViC B	EID7575
BRAF Mutation	Panitumumab + Cetuximab	Sensitivity/Response	CIViC B	EID1404
BRAF V600	Trametinib + Dabrafenib	Sensitivity/Response	CIViC B	EID1415
BRAF V600	Vemurafenib + Cetuximab	Sensitivity/Response	CIViC B	EID1598
BRAF V600	Encorafenib + Cetuximab	Sensitivity/Response	CIViC B	EID6046
BRAF V600	Cetuximab + Encorafenib + Alpelisib	Sensitivity/Response	CIViC B	EID6047
BRAF V600	Cetuximab + Vemurafenib + Irinotecan	Sensitivity/Response	CIViC B	EID7355
BRAF V600E	Erlotinib + Vemurafenib	Sensitivity/Response	CIViC B	EID11427
BRAF V600E	Cetuximab/Encorafenib Regimen	Sensitivity/Response	CIViC B	EID11436

+382 more predictive associations (showing top 30 by evidence level).