Malignant pancreatic neoplasm

disease

On this page

Also known as cancer of pancreasmalignant neoplasm of pancreasmalignant neoplasm of the pancreasmalignant pancreas neoplasmpancreas cancerpancreas neoplasmpancreatic cancerpancreatic tumour

Summary

Malignant pancreatic neoplasm (MONDO:0009831) is a cancer with 25 cohort genes (24 CIViC-evidence somatic drivers; 24 ClinVar predisposition records) and 2,765 clinical trials. The dominant Reactome pathway is Diseases of DNA repair (6 cohort genes). Molecularly, BRCA2 Mutation confers sensitivity to Rucaparib in Pancreatic Cancer (CIViC Level B); 54 further subtype–drug associations are mapped below. Top therapeutic interventions include oxaliplatin, gemcitabine, and irinotecan.

At a glance

Classification: Cancer
Cohort genes: 25
ClinVar variants: 24
Clinical trials: 2,765
Precision-medicine evidence (CIViC): 55 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	malignant pancreatic neoplasm
Mondo ID	MONDO:0009831
EFO	EFO:1000359
DOID	DOID:1793
ICD-10-CM	C25
ICD-11	542147910
NCIT	C9005
UMLS	C0346647
MedGen	138068
GARD	0027792
Anatomy (UBERON)	UBERON:0001264
Is cancer (heuristic)	yes

Also known as: cancer of pancreas · malignant neoplasm of pancreas · malignant neoplasm of the pancreas · malignant pancreas neoplasm · malignant pancreatic neoplasm · pancreas cancer · pancreas neoplasm · pancreatic cancer · pancreatic tumour

Data availability: 24 ClinVar variants · 8 GenCC gene-disease records.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › digestive system cancer › malignant pancreatic neoplasm

Subtypes (4): pancreas lymphoma, malignant exocrine pancreas neoplasm, pancreas sarcoma, pancreatic endocrine carcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

24 retrieved; paginated sample, class counts are floors:

9 conflicting classifications of pathogenicity, 9 pathogenic, 4 uncertain significance, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
428112	NM_000038.6(APC):c.4666dup (p.Thr1556fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
3035	NM_000051.4(ATM):c.3576G>A (p.Lys1192=)	ATM	Pathogenic	reviewed by expert panel
38043	NM_000059.4(BRCA2):c.6405_6409del (p.Asn2135fs)	BRCA2	Pathogenic	reviewed by expert panel
51659	NM_000059.4(BRCA2):c.4525C>T (p.Gln1509Ter)	BRCA2	Pathogenic	reviewed by expert panel
52086	NM_000059.4(BRCA2):c.6408_6414del (p.Asn2137fs)	BRCA2	Pathogenic	reviewed by expert panel
136132	NM_024675.4(PALB2):c.2167_2168del (p.Met723fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
4057204	NM_024675.4(PALB2):c.2973del (p.Val991_Met992insTer)	PALB2	Pathogenic	no assertion criteria provided
560017	NM_024675.4(PALB2):c.1652dup (p.Tyr551Ter)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
3384030	NM_005359.6(SMAD4):c.116_125del (p.Ala39fs)	SMAD4	Pathogenic	criteria provided, single submitter
125625	NM_007294.4(BRCA1):c.3327_3329del (p.Lys1110del)	BRCA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216241	NM_000059.4(BRCA2):c.2671G>C (p.Val891Leu)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
37845	NM_000059.4(BRCA2):c.353G>A (p.Arg118His)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41560	NM_000059.4(BRCA2):c.6325G>A (p.Val2109Ile)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
419387	NM_000059.4(BRCA2):c.10131A>C (p.Glu3377Asp)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
51049	NM_000059.4(BRCA2):c.10150C>T (p.Arg3384Ter)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
52347	NM_000059.4(BRCA2):c.7522G>A (p.Gly2508Ser)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
559995	NM_000059.4(BRCA2):c.9206G>A (p.Cys3069Tyr)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
96766	NM_000059.4(BRCA2):c.1568A>G (p.His523Arg)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
37593	NM_007294.4(BRCA1):c.4456A>T (p.Ser1486Cys)	BRCA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
559980	NM_007294.4(BRCA1):c.1769_1771del (p.Ser590del)	BRCA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
559982	NM_007294.4(BRCA1):c.4271A>G (p.Gln1424Arg)	BRCA1	Uncertain significance	no assertion criteria provided
224451	NM_000059.4(BRCA2):c.92G>T (p.Trp31Leu)	BRCA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
55720	NM_007294.4(BRCA1):c.811G>A (p.Val271Met)	BRCA1	Benign	reviewed by expert panel
51644	NM_000059.4(BRCA2):c.440A>G (p.Gln147Arg)	BRCA2	Benign	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 92 · Orphanet: 114 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
PALB2	LoF	OVT	CIViC #15013
FANCC			CIViC #1811
SMAD4	LoF	BRCA,CESC,CHOL,COAD,COADREAD,ESCA,ESCC,GBC,HNSC,LUAD,NSCLC,PAAD,PANCREAS,PRAD,PROSTATE,READ,STAD,STOMACH	CIViC #77
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69
RRM1			CIViC #5051
RRM2			CIViC #5052
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
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
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
SIRT1			CIViC #9538
ACVR1B	LoF	BRCA,COAD,COADREAD,LUAD,PAAD
CDK4	LoF	MEL	CIViC #13
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
MIR218-1			CIViC #24938
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
ETV4	Act	NBL	CIViC #1767
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
MLH1			CIViC #3532
MSH2			CIViC #3628
MSH6			CIViC #2478
PMS2	ambiguous	HCC	CIViC #4371
APC	LoF	AML,ANSC,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,HCC,LUAD,MEL,MT,NETNOS,NSCLC,PRAD,PROSTATE,READ,STAD,STOMACH,UM,VULVA	CIViC #66

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
CDK4	Definitive	Autosomal dominant	melanoma, cutaneous malignant, susceptibility to, 3	5
MLH1	Moderate	Autosomal dominant	malignant pancreatic neoplasm	19
MSH2	Moderate	Autosomal dominant	malignant pancreatic neoplasm	17
MSH6	Moderate	Autosomal dominant	malignant pancreatic neoplasm	17
PMS2	Moderate	Autosomal dominant	malignant pancreatic neoplasm	15
PRSS1	Moderate	Autosomal dominant	malignant pancreatic neoplasm	7
FANCC	Limited	Autosomal dominant	malignant pancreatic neoplasm	11
ACVR1B	No Known Disease Relationship	Unknown	malignant pancreatic neoplasm

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
PALB2	Orphanet:1333	Familial pancreatic carcinoma
PALB2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PALB2	Orphanet:178	Chordoma
PALB2	Orphanet:227535	Hereditary breast cancer
PALB2	Orphanet:84	Fanconi anemia
FANCC	Orphanet:84	Fanconi anemia
SMAD4	Orphanet:1333	Familial pancreatic carcinoma
SMAD4	Orphanet:2588	Myhre syndrome
SMAD4	Orphanet:329971	Generalized juvenile polyposis/juvenile polyposis coli
SMAD4	Orphanet:774	Hereditary hemorrhagic telangiectasia
SMAD4	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia
RRM1	Orphanet:254886	Autosomal recessive progressive external ophthalmoplegia
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

Cohort genes → proteins

25 cohort genes, 24 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	11
multi_evidence	14

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar,civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar,civic_evidence
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar,civic_evidence
FANCC	HGNC:3584	ENSG00000158169	Q00597	Fanconi anemia group C protein	gencc,civic_evidence
SMAD4	HGNC:6770	ENSG00000141646	Q13485	SMAD family member 4	clinvar,civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar,civic_evidence
RRM1	HGNC:10451	ENSG00000167325	P23921	Ribonucleoside-diphosphate reductase large subunit	civic_evidence
RRM2	HGNC:10452	ENSG00000171848	P31350	Ribonucleoside-diphosphate reductase subunit M2	civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
SIRT1	HGNC:14929	ENSG00000096717	Q96EB6	NAD-dependent protein deacetylase sirtuin-1	civic_evidence
ACVR1B	HGNC:172	ENSG00000135503	P36896	Activin receptor type-1B	gencc
CDK4	HGNC:1773	ENSG00000135446	P11802	Cyclin-dependent kinase 4	gencc
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	civic_evidence
MIR218-1	HGNC:31595	ENSG00000207732		microRNA 218-1	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
ETV4	HGNC:3493	ENSG00000175832	P43268	ETS translocation variant 4	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	gencc
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	gencc
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	gencc
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	gencc
PRSS1	HGNC:9475	ENSG00000204983	P07477	Serine protease 1	gencc
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
PALB2	Partner and localizer of BRCA2	Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
FANCC	Fanconi anemia group C protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
SMAD4	SMAD family member 4	In muscle physiology, plays a central role in the balance between atrophy and hypertrophy.
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.
RRM1	Ribonucleoside-diphosphate reductase large subunit	Provides the precursors necessary for DNA synthesis.
RRM2	Ribonucleoside-diphosphate reductase subunit M2	Provides the precursors necessary for DNA synthesis.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
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…
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
SIRT1	NAD-dependent protein deacetylase sirtuin-1	NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolis…
ACVR1B	Activin receptor type-1B	Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B).
CDK4	Cyclin-dependent kinase 4	Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition.
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.
ETV4	ETS translocation variant 4	Transcriptional activator.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
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).
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
PRSS1	Serine protease 1	Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec.
APC	Adenomatous polyposis coli protein	Tumor suppressor.

Protein-family classification

Druggable: 11 · Difficult: 4 · Unknown: 10 · Druggable fraction: 0.44

Family distribution

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

Family	Genes	Fold	FDR
Kinase	6	6.7×	0.001
Enzyme (other)	4	1.9×	0.452
Protease	1	1.5×	0.750
Scaffold/PPI	2	1.4×	0.750
Other/Unknown	10	0.7×	0.963
Transcription factor	2	0.7×	0.963

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
FANCC	Other/Unknown	no		FANCC
SMAD4	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
RRM1	Enzyme (other)	yes	1.17.4.1	RNR_lg_C, ATP-cone_dom, RNR_R1-su_N
RRM2	Enzyme (other)	yes	1.17.4.1	RNR_small_fam, Ferritin-like_SF, RNR-like
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
STK11	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
SIRT1	Enzyme (other)	yes	2.3.1.286	Sirtuin, Ssirtuin_cat_dom, Sirtuin_cat_small_dom_sf
ACVR1B	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
CDK4	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
MIR218-1	Other/Unknown	no
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ETV4	Other/Unknown	no		Ets_dom, ETS_PEA3_N, WH-like_DNA-bd_sf
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
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
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
PRSS1	Protease	yes		Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP

Expression context

Cohort genes with no expression data: 0.

23 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)	25
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	10
ganglionic eminence	6
secondary oocyte	5
calcaneal tendon	5
male germ line stem cell (sensu Vertebrata) in testis	4
oocyte	4
primordial germ cell in gonad	2
buccal mucosa cell	2
colonic epithelium	2
cervix squamous epithelium	2
embryo	2
pancreatic ductal cell	1
right lobe of liver	1
corpus callosum	1
hindlimb stylopod muscle	1
left testis	1
right testis	1
tendon of biceps brachii	1
middle temporal gyrus	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
FANCC	195	ubiquitous	marker	pancreatic ductal cell, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis
SMAD4	288	ubiquitous	marker	ventricular zone, ganglionic eminence, calcaneal tendon
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
RRM1	296	ubiquitous	marker	ventricular zone, ganglionic eminence, cervix squamous epithelium
RRM2	233	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
SIRT1	280	ubiquitous	marker	calcaneal tendon, ganglionic eminence, ventricular zone
ACVR1B	296	ubiquitous	marker	secondary oocyte, oocyte, middle temporal gyrus
CDK4	138	ubiquitous	marker	embryo, ganglionic eminence, ventricular zone
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
MIR218-1	66		yes	kidney, calcaneal tendon, adrenal tissue
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
ETV4	171	ubiquitous	marker	primordial germ cell in gonad, type B pancreatic cell, olfactory bulb
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
MLH1	296	ubiquitous	marker	tibialis anterior, skeletal muscle tissue of rectus abdominis, deltoid
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
PRSS1	127	tissue_specific	marker	body of pancreas, pancreas, islet of Langerhans
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 53.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
KRAS	14,509
ERBB2	9,659
CDKN2A	9,311
BRCA1	9,064
CDK4	8,412
SIRT1	8,285
BRAF	7,394
ATM	7,383
SMAD4	7,320

Intra-cohort edges

A	B	Sources
ACVR1B	SMAD4	intact, string_interaction
ATM	BRCA1	string_interaction
ATM	BRCA2	string_interaction
ATM	MLH1	string_interaction
ATM	MSH2	string_interaction
ATM	MSH6	string_interaction
ATM	STK11	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	CDKN2A	string_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MLH1	string_interaction
BRAF	PMS2	string_interaction
BRAF	TP53	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	MLH1	string_interaction
BRCA1	MSH2	string_interaction
BRCA1	MSH6	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	PMS2	string_interaction
BRCA1	TP53	string_interaction
BRCA2	FANCC	string_interaction
BRCA2	MLH1	string_interaction
BRCA2	MSH2	string_interaction
BRCA2	MSH6	string_interaction
BRCA2	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	PMS2	string_interaction
BRCA2	PRSS1	string_interaction
BRCA2	STK11	string_interaction
BRCA2	TP53	string_interaction
CDK4	CDKN2A	biogrid_interaction, intact, string_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	TP53	string_interaction
ERBB2	KRAS	string_interaction
ETV4	STK11	biogrid_interaction
FANCC	PALB2	string_interaction
FANCC	SMAD4	intact
KRAS	STK11	string_interaction
KRAS	TP53	string_interaction
MLH1	MSH2	string_interaction
MLH1	MSH6	string_interaction
MLH1	PMS2	biogrid_interaction, intact, string_interaction
MSH2	MSH6	biogrid_interaction, intact, string_interaction
MSH2	PMS2	string_interaction
MSH6	PMS2	string_interaction
PALB2	PRSS1	string_interaction
PALB2	STK11	string_interaction
PRSS1	STK11	string_interaction
RRM1	RRM2	biogrid_interaction, intact, string_interaction
SIRT1	STK11	biogrid_interaction

Structural data

PDB: 24 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
BRAF	P15056	131
ERBB2	P04626	63
BRCA1	P38398	33
APC	P25054	31
MSH2	P43246	30
CDK4	P11802	15
BRCA2	P51587	14
ATM	Q13315	14
SMAD4	Q13485	12
RRM1	P23921	12
PRSS1	P07477	12
SIRT1	Q96EB6	9
PMS2	P54278	9
MSH6	P52701	8
MLH1	P40692	7
FANCC	Q00597	6
RRM2	P31350	5
CDKN2A	P42771	5
PALB2	Q86YC2	4
STK11	Q15831	4
ETV4	P43268	3
ACVR1B	P36896	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 382. Enrichment computed across 25 evidence-associated genes (24 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 24 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Diseases of DNA repair	6	142.8×	6e-10	BRCA1, BRCA2, ATM, MLH1, MSH2, MSH6
TP53 Regulates Transcription of DNA Repair Genes	7	52.9×	7e-09	BRCA1, FANCC, ATM, TP53, MLH1, MSH2, PMS2
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	4	135.9×	2e-06	MLH1, MSH2, MSH6, PMS2
Meiosis	5	59.5×	2e-06	BRCA1, BRCA2, ATM, CDK4, MLH1
Mismatch Repair	3	356.9×	2e-06	MLH1, MSH2, MSH6
Diseases of Mismatch Repair (MMR)	3	356.9×	2e-06	MLH1, MSH2, MSH6
DNA Repair	6	24.6×	6e-06	BRCA1, BRCA2, ATM, MLH1, MSH2, MSH6
Reproduction	5	39.6×	6e-06	BRCA1, BRCA2, ATM, CDK4, MLH1
Impaired BRCA2 binding to PALB2	4	76.1×	8e-06	BRCA1, BRCA2, PALB2, ATM
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	4	70.5×	8e-06	BRCA1, BRCA2, PALB2, ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	4	70.5×	8e-06	BRCA1, BRCA2, PALB2, ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	4	70.5×	8e-06	BRCA1, BRCA2, PALB2, ATM
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	4	65.6×	1e-05	BRCA1, BRCA2, PALB2, ATM
Homologous DNA Pairing and Strand Exchange	4	63.4×	1e-05	BRCA1, BRCA2, PALB2, ATM
RNA Polymerase II Transcription	9	8.4×	1e-05	BRCA1, SMAD4, ATM, STK11, SIRT1, CDK4, CDKN2A, MLH1 (+1 more)
Disease	11	6.0×	1e-05	BRCA1, BRCA2, SMAD4, ATM, BRAF, CDK4, CDKN2A, APC (+3 more)
Meiotic recombination	5	27.0×	2e-05	BRCA1, BRCA2, ATM, CDK4, MLH1
Resolution of D-loop Structures through Holliday Junction Intermediates	4	50.1×	2e-05	BRCA1, BRCA2, PALB2, ATM
Defective homologous recombination repair (HRR) due to PALB2 loss of function	3	119.0×	3e-05	BRCA1, BRCA2, ATM
Transcriptional Regulation by TP53	6	15.5×	3e-05	BRCA1, ATM, STK11, CDKN2A, MLH1, MSH2
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	3	102.0×	5e-05	MLH1, MSH2, PMS2
Diseases of DNA Double-Strand Break Repair	3	102.0×	5e-05	BRCA1, BRCA2, ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	3	102.0×	5e-05	BRCA1, BRCA2, ATM
Gene expression (Transcription)	9	6.7×	5e-05	BRCA1, SMAD4, ATM, STK11, SIRT1, CDK4, CDKN2A, MLH1 (+1 more)
Defective Mismatch Repair Associated With MLH1	2	475.8×	5e-05	MLH1, PMS2
Defective Mismatch Repair Associated With MSH6	2	475.8×	5e-05	MSH2, MSH6
Defective Mismatch Repair Associated With PMS2	2	475.8×	5e-05	MLH1, PMS2
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	2	475.8×	5e-05	CDK4, CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	2	475.8×	5e-05	CDK4, CDKN2A
Stabilization of p53	3	95.2×	5e-05	ATM, TP53, CDKN2A

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
somatic recombination of immunoglobulin gene segments	3	526.6×	2e-06	MSH2, MSH6, PMS2
somatic hypermutation of immunoglobulin genes	4	175.5×	2e-06	MLH1, MSH2, MSH6, PMS2
negative regulation of cell growth	6	36.0×	2e-06	BRCA1, SMAD4, STK11, TP53, ACVR1B, CDKN2A
positive regulation of isotype switching to IgA isotypes	3	351.1×	6e-06	MLH1, MSH2, PMS2
mismatch repair	4	108.0×	6e-06	MLH1, MSH2, MSH6, PMS2
double-strand break repair	5	42.3×	1e-05	BRCA1, BRCA2, ATM, TP53, MSH2
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	4	82.6×	1e-05	BRCA2, TP53, SIRT1, MSH2
determination of adult lifespan	4	72.0×	2e-05	ATM, TP53, MSH2, MSH6
response to ionizing radiation	4	68.5×	2e-05	BRCA1, ATM, RRM1, STK11
cellular response to ionizing radiation	4	68.5×	2e-05	BRCA1, BRCA2, TP53, SIRT1
positive regulation of isotype switching to IgG isotypes	3	191.5×	2e-05	MLH1, MSH2, PMS2
regulation of cell cycle	6	18.6×	3e-05	BRCA1, ATM, STK11, TP53, CDK4, CDKN2A
positive regulation of cellular senescence	3	162.0×	3e-05	TP53, SIRT1, KRAS
intrinsic apoptotic signaling pathway in response to DNA damage	4	54.0×	3e-05	BRCA1, ATM, MLH1, MSH6
cellular senescence	4	49.3×	5e-05	BRCA2, ATM, TP53, CDKN2A
DNA repair	6	16.0×	6e-05	BRCA1, FANCC, RRM1, RRM2, MSH2, MSH6
replicative senescence	3	123.9×	6e-05	ATM, TP53, CDKN2A
positive regulation of gene expression	7	11.3×	6e-05	BRCA1, SMAD4, ATM, BRAF, TP53, ACVR1B, KRAS
response to X-ray	3	110.9×	8e-05	BRCA2, TP53, MSH2
isotype switching	3	105.3×	8e-05	MLH1, MSH2, MSH6
DNA damage response	6	13.4×	1e-04	BRCA1, ATM, STK11, TP53, SIRT1, APC
ribonucleoside diphosphate metabolic process	2	468.1×	1e-04	RRM1, RRM2
deoxyribonucleotide biosynthetic process	2	468.1×	1e-04	RRM1, RRM2
2’-deoxyribonucleotide biosynthetic process	2	468.1×	1e-04	RRM1, RRM2
positive regulation of macrophage apoptotic process	2	468.1×	1e-04	SIRT1, CDKN2A
double-strand break repair via homologous recombination	4	26.0×	4e-04	BRCA1, BRCA2, PALB2, ATM
negative regulation of mammary gland epithelial cell proliferation	2	280.9×	4e-04	BRCA2, CDKN2A
negative regulation of immature T cell proliferation in thymus	2	234.1×	6e-04	CDKN2A, ERBB2
nucleotide-excision repair	3	47.9×	7e-04	BRCA2, FANCC, TP53
somitogenesis	3	46.8×	7e-04	PALB2, ATM, TP53

Therapeutics

Drugs indicated for this disease

1 approved, 12 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Paclitaxel	Approved (phase 4)
Albumin Human	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
Erlotinib	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Fluzoparib	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Gimeracil	Phase 3 (in late-stage trials)
Nimotuzumab	Phase 3 (in late-stage trials)
Oteracil	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Tegafur	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Atezolizumab, Cabozantinib, Catequentinib, Digoxin, Endostatin, N-Terminal-Mggshhhhh, Envafolimab, Galeterone, Ipilimumab, Metformin, Nivolumab, Nogapendekin Alfa, Panitumumab, Paricalcitol, Pembrolizumab, Penpulimab, Pimicotinib, Rivoceranib, Serplulimab, Simvastatin, Sintilimab, Sorafenib, Surufatinib, Tipiracil, Toripalimab, Zimberelimab.

Drug target analysis

Approved (phase 4): 11 · Phase ≥3: 13 · Phased (≥1): 14 · Undrugged: 11

Druggability breadth: 19 of 25 evidence-associated genes (76%) 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
BRCA1	RIBOFLAVIN
ATM	AMIODARONE HYDROCHLORIDE
BRAF	VEMURAFENIB
STK11	FEDRATINIB
TP53	NITROFURANTOIN
SIRT1	NIACINAMIDE
ACVR1B	FEDRATINIB
CDK4	PALBOCICLIB
ERBB2	CLOTRIMAZOLE
KRAS	VEMURAFENIB
PRSS1	ARGATROBAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ERBB2	83	4
CDK4	56	4
BRAF	48	4
ATM	35	4
ACVR1B	21	4
STK11	17	4
PRSS1	17	4
BRCA1	12	4
KRAS	11	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, ERBB2
FEDRATINIB	4	ACVR1B, BRAF, CDK4, STK11
SORAFENIB	4	BRAF, ERBB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
CDK4	1,142	Binding:1086, Functional:53, ADMET:2, Toxicity:1
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
PRSS1	674	Binding:616, ADMET:51, Functional:7
SIRT1	645	Binding:642, ADMET:3
ACVR1B	286	Binding:282, ADMET:3, Functional:1
STK11	244	Binding:244
ATM	240	Binding:233, Functional:5, ADMET:2
RRM1	83	Binding:80, Functional:3
RRM2	37	Binding:34, Functional:3
APC	24	Binding:24
BRCA1	13	Binding:9, Functional:4
MSH6	10	Binding:10
MSH2	9	Binding:9
SMAD4	6	Binding:6
CDKN2A	2	Binding:2
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
RRM1	1.17.4.1	ribonucleoside-diphosphate reductase
RRM2	1.17.4.1	ribonucleoside-diphosphate reductase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
SIRT1	2.3.1.286	protein acetyllysine N-acetyltransferase
ACVR1B	2.7.10.2	non-specific protein-tyrosine kinase
CDK4	2.7.11.22	cyclin-dependent kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ATM	240
BRAF	1,442
STK11	244
TP53	869
SIRT1	645
ACVR1B	286
CDK4	1,142
ERBB2	1,221
KRAS	861
PRSS1	674

Pharmacogenomics

Cohort genes with a PharmGKB record: 25; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

29 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, ERBB2
FEDRATINIB	4	ACVR1B, BRAF, CDK4, STK11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	11	BRCA1, ATM, BRAF, STK11, TP53, SIRT1, ACVR1B, CDK4, ERBB2, KRAS (+1 more)
B	Phased (≥1) drug, not yet approved	3	RRM1, RRM2, MSH6
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	11	BRCA2, PALB2, FANCC, SMAD4, CDKN2A, MIR218-1, ETV4, MLH1, MSH2, PMS2 (+1 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
PALB2	0	BRCA1
CDKN2A	2	CDK4
MLH1	0	MSH6
PMS2	1	MSH6
FANCC	0	—
SMAD4	6	—
MIR218-1	0	—
ETV4	0	—
MSH2	9	—
APC	24	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,765.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	655
PHASE1/PHASE2	250
PHASE3	135
PHASE4	31
PHASE2/PHASE3	29

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04025840	PHASE4	ACTIVE_NOT_RECRUITING	Perioperative Epidural Block and Dexamethasone in Pancreatic Cancer Surgery
NCT05035147	PHASE4	RECRUITING	Albumin-bound Paclitaxel Combined With Gemcitabine First-line Inoperable Pancreatic Cancer
NCT05245877	PHASE4	RECRUITING	Pre- Vs. Postoperative Thromboprophylaxis in Pancreatic Surgery
NCT05784311	PHASE4	RECRUITING	Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)
NCT06779318	PHASE4	NOT_YET_RECRUITING	Maintenance Chemotherapy With S-1 vs. Observation After Adjuvant Therapy for Resected Pancreatic Cancer With High Risk of Recurrence/Metastasis
NCT07557394	PHASE4	NOT_YET_RECRUITING	A Prospective Non-randomized Controlled Interventional Study on the Effect of Shouhui Tongbian Capsules Combined With Pancreatin Enteric-coated Capsules on Pancreatic Exocrine Function in Patients After Curative Resection for Pancreatic Cancer
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00578279	PHASE4	COMPLETED	Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN)With Alcohol in Unresectable Pancreatic Cancer: a Pilot Study
NCT00583479	PHASE4	COMPLETED	Prospective Study of Celiac Block Injection: 1 vs. 2
NCT00642733	PHASE4	TERMINATED	A Study of First Line Treatment With Tarceva (Erlotinib) in Combination With Gemcitabine in Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00920023	PHASE4	COMPLETED	Pre-Operative Staging of Pancreatic Cancer Using Superparamagnetic Iron Oxide Magnetic Resonance Imaging (SPIO MRI)
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT01041612	PHASE4	COMPLETED	Comparing Covered Self-expandable Metallic Stent (SEMS) Above/Across the Sphincter of Oddi
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT01768988	PHASE4	TERMINATED	Efficacy Of Pregabalin In The Treatment Of Pancreatic Cancer Pain. A Randomized Controlled Double-Blind, Parallel Group Study
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02044224	PHASE4	COMPLETED	Effects of Dexmedetomidine During IRE Procedures for Solid Tumours
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03891979	PHASE4	WITHDRAWN	Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma
NCT04058236	PHASE4	UNKNOWN	Glycocalyx Levels in Patients Undergoing Pancreatectomy
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04217096	PHASE4	UNKNOWN	Efficacy and Safety of Paclitaxel Liposome and S-1 as First-line Therapy in \ Advanced Pancreatic Cancer Patients
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04809935	PHASE4	UNKNOWN	EUS-Coeliac Plexus Block Versus Radiofrequency Ablation in Pain Relief of Patients With Malignancy
NCT06316908	PHASE4	COMPLETED	Permanent Celiac Plexus Block: Comparison of Pain Score in Unilateral and Bilateral Posterior Percutaneous Approach
NCT02000089	PHASE3	RECRUITING	The Cancer of the Pancreas Screening-5 CAPS5)Study
NCT02919787	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Nordic Pancreatic Cancer Trial (NorPACT) - 1
NCT03257033	PHASE3	RECRUITING	Intra-arterial Gemcitabine vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC
NCT03755739	PHASE2/PHASE3	RECRUITING	Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors
NCT03899636	PHASE3	ACTIVE_NOT_RECRUITING	A Pivotal Study of Safety and Effectiveness of NanoKnife IRE for Stage 3 Pancreatic Cancer
NCT04340141	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer
NCT04927780	PHASE3	ACTIVE_NOT_RECRUITING	Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer
NCT05254171	PHASE2/PHASE3	RECRUITING	Study of Nab-Paclitaxel and Gemcitabine With or Without SBP-101 in Pancreatic Cancer
NCT05653453	PHASE3	RECRUITING	Clinical Study of Tumor Treating Fields Combined with Gemcitabine and Albumin-bound Paclitaxel in the First-line Treatment of Locally Advanced Pancreatic Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
OXALIPLATIN	4	78
GEMCITABINE	4	37
IRINOTECAN	4	19
ERLOTINIB	4	14
LEUCOVORIN	4	10
SARGRAMOSTIM	4	7
SORAFENIB	4	7
FLUOROURACIL	4	6
CAPECITABINE	4	5
DALTEPARIN SODIUM	4	5
PANITUMUMAB	4	5
DASATINIB ANHYDROUS	4	4
MITOMYCIN	4	4
RUXOLITINIB	4	3
SELUMETINIB	4	3
ALBUMIN HUMAN	4	2
ALCOHOL	4	2
CALCITRIOL	4	2
EPIRUBICIN HYDROCHLORIDE	4	2
IXABEPILONE	4	2
PACLITAXEL	4	2
PAZOPANIB	4	2
STREPTOZOCIN	4	2
TIPIRACIL HYDROCHLORIDE	4	2
VISMODEGIB	4	2
VORINOSTAT	4	2
ALDESLEUKIN	4	1
ARSENIC TRIOXIDE	4	1
BEVACIZUMAB	4	1
BUPROPION HYDROCHLORIDE	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 55 predictive associations from 61 curated evidence items; also 10 prognostic, 3 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
BRCA2 Mutation	Rucaparib	Sensitivity/Response	CIViC B	EID7436 +3
BRCA1 Mutation	Rucaparib	Sensitivity/Response	CIViC B	EID9291 +1
RRM1 Underexpression	Gemcitabine	Sensitivity/Response	CIViC B	EID5506 +1
BRCA1 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID5914
BRCA1 Mutation	Cisplatin + Oxaliplatin	Sensitivity/Response	CIViC B	EID5915
BRCA1 Mutation	Cisplatin + Gemcitabine + Veliparib	Sensitivity/Response	CIViC B	EID5932
BRCA1 Mutation	Veliparib	Sensitivity/Response	CIViC B	EID5934
BRCA2 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID5913
BRCA2 Mutation	Platinum Compound	Sensitivity/Response	CIViC B	EID5916
BRCA2 Mutation	Cisplatin + Gemcitabine + Veliparib	Sensitivity/Response	CIViC B	EID5933
BRCA2 Mutation	Veliparib	Sensitivity/Response	CIViC B	EID5935
CDKN2A Loss OR CDKN2A Mutation	Palbociclib	Sensitivity/Response	CIViC B	EID11653
CDKN2A Mutation	Palbociclib	Sensitivity/Response	CIViC B	EID7299
ERBB2 Amplification	Trastuzumab + Pertuzumab	Sensitivity/Response	CIViC B	EID5985
ERBB2 Overexpression	Trastuzumab + Capecitabine	Sensitivity/Response	CIViC B	EID5955
ERBB2 Overexpression	Trastuzumab + Gemcitabine	Sensitivity/Response	CIViC B	EID5956
KRAS Activating Mutation	Salirasib	Sensitivity/Response	CIViC B	EID7180
KRAS G12C	Sotorasib	Sensitivity/Response	CIViC B	EID11680
PALB2 Mutation	Rucaparib	Sensitivity/Response	CIViC B	EID9294
TP53 Mutation	Gemcitabine	Sensitivity/Response	CIViC B	EID8282
KRAS Exon 2 Mutation	Erlotinib + Gemcitabine	Resistance	CIViC B	EID1219
NTRK1 Fusion	Larotrectinib	Sensitivity/Response	CIViC C	EID6051 +1
BRAF N486_P490del	Trametinib	Sensitivity/Response	CIViC C	EID7730
BRAF V600E AND ERBB2 Amplification AND SMAD4 LOSS AND TP53 V218E	Trastuzumab + Bevacizumab + Lapatinib + Trametinib	Sensitivity/Response	CIViC C	EID11712
BRCA2 Mutation	Iniparib	Sensitivity/Response	CIViC C	EID5936
CUX1::BRAF Fusion	Vemurafenib	Sensitivity/Response	CIViC C	EID5977
KRAS G12D AND CDKN2A p16 R80*	Trametinib + Afatinib + Palbociclib	Sensitivity/Response	CIViC C	EID11713
KRAS G12D AND GNAS R201C AND NF1 D1976fs	Trametinib	Sensitivity/Response	CIViC C	EID11714
KRAS G12D AND KRAS G12R AND CDKN2A Loss AND CDKN2B Loss AND SMAD4 Deletion AND TP53 R267W	Trametinib + Palbociclib + Bevacizumab	Sensitivity/Response	CIViC C	EID11711
KRAS G12D AND KRAS G12R AND CDKN2A Loss AND CDKN2B Loss AND TP53 R267W	Palbociclib + Trametinib + Bevacizumab	Sensitivity/Response	CIViC C	EID11710

+25 more predictive associations (showing top 30 by evidence level).

Cohort genes: BRCA1, BRCA2, PALB2, FANCC, SMAD4, ATM, RRM1, RRM2, BRAF, STK11, TP53, SIRT1, ACVR1B, CDK4, CDKN2A, MIR218-1, ERBB2, ETV4, KRAS, MLH1, MSH2, MSH6, PMS2, APC, PRSS1
Drugs: Oxaliplatin, Gemcitabine, Irinotecan, Erlotinib, Sargramostim, Sorafenib, Fluorouracil, Capecitabine, Dalteparin, Panitumumab, Dasatinib, Mitomycin, Ruxolitinib, Selumetinib, Albumin Human, Alcohol, Calcitriol, Epirubicin, Ixabepilone, Paclitaxel, Pazopanib, Streptozocin, Tipiracil, Vismodegib, Vorinostat, Aldesleukin, Arsenic Trioxide, Bevacizumab, Bupropion, Rucaparib, Olaparib, Veliparib, Palbociclib, Sotorasib, Larotrectinib, Trametinib, Iniparib, Vemurafenib