Pancreatic adenocarcinoma

Summary

Pancreatic adenocarcinoma (MONDO:0006047) is a disease (an umbrella term covering 5 Mondo subtypes) with 13 cohort genes and 584 clinical trials. The dominant Reactome pathway is Signaling by ERBB2 ECD mutants (3 cohort genes). Molecularly, BRCA1 Loss-of-function confers sensitivity to Olaparib in Pancreatic Adenocarcinoma (CIViC Level A); 18 further subtype–drug associations are mapped below. Top therapeutic interventions include capecitabine, gemcitabine, and paricalcitol.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 13
• ClinVar variants: 685
• Clinical trials: 584
• Precision-medicine evidence (CIViC): 19 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pancreatic adenocarcinoma
Mondo ID	MONDO:0006047
EFO	EFO:1000044
DOID	DOID:4074
ICD-11	1663659989
NCIT	C8294
SNOMED CT	700423003
UMLS	C0281361
MedGen	83800
GARD	0027736
Anatomy (UBERON)	UBERON:0001264
Is cancer (heuristic)	no

Also known as: adenocarcinoma - pancreas · adenocarcinoma of pancreas · adenocarcinoma of the pancreas · PAAD · pancreas adenocarcinoma · pancreatic adenocarcinoma

Data availability: 685 ClinVar variants · 123 cell lines · 64 intOGen driver records.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › adenocarcinoma › pancreatic adenocarcinoma

Related subtypes (63): epididymal adenocarcinoma, rete testis adenocarcinoma, seminal vesicle adenocarcinoma, ethmoid sinus adenocarcinoma, lacrimal gland adenocarcinoma, papillary adenocarcinoma, fallopian tube adenocarcinoma, bladder adenocarcinoma, ovarian adenocarcinoma, trabecular adenocarcinoma, middle ear adenocarcinoma, bile duct adenocarcinoma, granular cell carcinoma, small intestine adenocarcinoma, urethra adenocarcinoma, villous adenocarcinoma, thymus gland adenocarcinoma, nasal cavity adenocarcinoma, ureter adenocarcinoma, adenocarcinoma in situ, gastroesophageal junction adenocarcinoma, maxillary sinus adenocarcinoma, mucinous adenocarcinoma, acinar cell carcinoma, adenoid cystic carcinoma, breast adenocarcinoma, clear cell adenocarcinoma, colorectal adenocarcinoma, endometrioid adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, prostate adenocarcinoma, renal cell carcinoma, signet ring cell carcinoma, cervical adenocarcinoma, serous adenocarcinoma, endometrium adenocarcinoma, sweat gland carcinoma, cystadenocarcinoma, tubular adenocarcinoma, mesonephric adenocarcinoma, scirrhous adenocarcinoma, follicular variant thyroid gland papillary carcinoma, gallbladder adenocarcinoma, hepatoid adenocarcinoma, intestinal type adenocarcinoma, micropapillary serous carcinoma, minor salivary gland adenocarcinoma, poorly differentiated thyroid gland carcinoma, salivary gland basal cell adenocarcinoma, submandibular gland adenocarcinoma, sebaceous adenocarcinoma, hepatocellular carcinoma, parathyroid gland carcinoma, pituitary adenocarcinoma, vaginal adenocarcinoma, Paget disease, diffuse type adenocarcinoma, vulvar adenocarcinoma, thyroid gland adenocarcinoma, gastroesophageal adenocarcinoma, adenoacanthoma

Subtypes (5): pancreatic cystadenocarcinoma, pancreatic intraductal papillary-mucinous neoplasm with an associated invasive carcinoma, pancreatic ductal adenocarcinoma, pancreatic acinar cell carcinoma, mucinous pancreas adenocarcinoma

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

600 retrieved; paginated sample, class counts are floors:

351 uncertain significance, 194 likely benign, 22 conflicting classifications of pathogenicity, 17 benign, 16 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1038184	NM_001166108.2(PALLD):c.2340A>C (p.Glu780Asp)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1125873	NM_001166108.2(PALLD):c.2961C>T (p.Ile987=)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136014	NM_001166108.2(PALLD):c.2393T>C (p.Met798Thr)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1407833	NM_001166108.2(PALLD):c.3357C>T (p.Tyr1119=)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1797740	NM_001166108.2(PALLD):c.2975C>T (p.Thr992Met)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188283	NM_001166108.2(PALLD):c.*153A>G	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216529	NM_001166108.2(PALLD):c.2513G>A (p.Ser838Asn)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
238607	NM_001166108.2(PALLD):c.2723G>A (p.Arg908His)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348044	NM_001166108.2(PALLD):c.2891A>C (p.Asp964Ala)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
476380	NM_001166108.2(PALLD):c.3087T>A (p.Phe1029Leu)	CBR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1045446	NM_001166108.2(PALLD):c.1965-12772T>C	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1141572	NM_001166108.2(PALLD):c.1965-12735C>G	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1169427	NM_001166108.2(PALLD):c.1965-12701GCC[4]	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128101	NM_001166108.2(PALLD):c.2084T>G (p.Leu695Arg)	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136001	NM_001166108.2(PALLD):c.1965-12840C>G	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136003	NM_001166108.2(PALLD):c.1965-12812C>A	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136007	NM_001166108.2(PALLD):c.1965-12594T>G	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188331	NM_001166108.2(PALLD):c.1965-13000G>T	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216534	NM_001166108.2(PALLD):c.1965-12907G>A	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2192174	NM_001166108.2(PALLD):c.1965-12663C>T	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2572	NM_001166108.2(PALLD):c.1965-12616C>T	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3610573	NM_001166108.2(PALLD):c.1965-12835G>A	PALLD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000125	NM_001166108.2(PALLD):c.2542G>A (p.Asp848Asn)	CBR4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1000574	NM_001166108.2(PALLD):c.2549C>A (p.Thr850Asn)	CBR4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1007249	NM_001166108.2(PALLD):c.2914A>G (p.Ser972Gly)	CBR4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1009730	NM_001166108.2(PALLD):c.2399T>C (p.Leu800Pro)	CBR4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014338	NM_001166108.2(PALLD):c.2294T>C (p.Ile765Thr)	CBR4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014538	NM_001166108.2(PALLD):c.2158G>A (p.Val720Ile)	CBR4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1015523	NM_001166108.2(PALLD):c.3046C>T (p.Leu1016Phe)	CBR4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1018475	NM_001166108.2(PALLD):c.3254G>C (p.Cys1085Ser)	CBR4	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 65 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
ERBB2	Orphanet:213726	Serous carcinoma of the corpus uteri
ERBB2	Orphanet:2800	Extramammary Paget disease
ERBB2	Orphanet:388	Hirschsprung disease
ERBB2	Orphanet:99976	Adenocarcinoma of the oesophagus and oesophagogastric junction
IGF2	Orphanet:2128	Isolated hemihyperplasia
IGF2	Orphanet:231117	Beckwith-Wiedemann syndrome due to imprinting defect of 11p15
IGF2	Orphanet:231140	Silver-Russell syndrome due to an imprinting defect of 11p15
IGF2	Orphanet:231144	Silver-Russell syndrome due to 11p15 microduplication
IGF2	Orphanet:397590	Silver-Russell syndrome due to a point mutation
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome

Cohort genes → proteins

13 cohort genes, 13 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	11
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	civic_evidence
SLC29A1	HGNC:11003	ENSG00000112759	Q99808	Equilibrative nucleoside transporter 1	civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
HIF1A	HGNC:4910	ENSG00000100644	Q16665	Hypoxia-inducible factor 1-alpha	civic_evidence
IGF2	HGNC:5466	ENSG00000167244	P01344	Insulin-like growth factor 2	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
SMAD4	HGNC:6770	ENSG00000141646	Q13485	SMAD family member 4	civic_evidence
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	civic_evidence
PALLD	HGNC:17068	ENSG00000129116	Q8WX93	Palladin	clinvar
CBR4	HGNC:25891	ENSG00000145439	Q8N4T8	3-oxoacyl-[acyl-carrier-protein] reductase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
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.
SLC29A1	Equilibrative nucleoside transporter 1	Uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
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.
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.
HIF1A	Hypoxia-inducible factor 1-alpha	Functions as a master transcriptional regulator of the adaptive response to hypoxia.
IGF2	Insulin-like growth factor 2	The insulin-like growth factors possess growth-promoting activity.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
SMAD4	SMAD family member 4	In muscle physiology, plays a central role in the balance between atrophy and hypertrophy.
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.
PALLD	Palladin	Cytoskeletal protein required for organization of normal actin cytoskeleton.
CBR4	3-oxoacyl-[acyl-carrier-protein] reductase	Component of the heterotetramer complex KAR (3-ketoacyl-[acyl carrier protein] reductase or 3-ketoacyl-[ACP] reductase) that forms part of the mitochondrial fatty acid synthase (mtFAS).

Protein-family classification

Druggable: 6 · Difficult: 2 · Unknown: 5 · Druggable fraction: 0.46

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	3	6.4×	0.061
Transporter	1	6.0×	0.465
Antibody/Immunoglobulin	1	2.2×	0.718
Transcription factor	2	1.3×	0.718
Enzyme (other)	1	0.9×	0.813
Other/Unknown	5	0.7×	0.938

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
SLC29A1	Transporter	yes		Eqnu_transpt, ENT1/ENT2, MFS_trans_sf
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, 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
HIF1A	Transcription factor	no		PAS, HIF-1_alpha, PAC
IGF2	Other/Unknown	no		IGF2_C, Insulin-like, IGF2
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
SMAD4	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_dom
PALLD	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
CBR4	Other/Unknown	no		SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf

Expression context

Cohort genes with no expression data: 0.

13 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	3
ventricular zone	3
male germ line stem cell (sensu Vertebrata) in testis	2
secondary oocyte	2
nipple	2
sural nerve	2
buccal mucosa cell	1
colonic epithelium	1
primordial germ cell in gonad	1
apex of heart	1
mucosa of stomach	1
right coronary artery	1
gingiva	1
gingival epithelium	1
lower esophagus mucosa	1
right uterine tube	1
corpus epididymis	1
epithelial cell of pancreas	1
pancreatic ductal cell	1
adrenal tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
SLC29A1	235	ubiquitous	marker	mucosa of stomach, right coronary artery, apex of heart
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
HIF1A	295	ubiquitous	marker	pancreatic ductal cell, epithelial cell of pancreas, corpus epididymis
IGF2	135	ubiquitous	marker	adrenal tissue, placenta, sural nerve
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
SMAD4	288	ubiquitous	marker	ventricular zone, ganglionic eminence, calcaneal tendon
RB1	287	ubiquitous	marker	epithelium of nasopharynx, choroid plexus epithelium, visceral pleura
PALLD	302	ubiquitous	marker	saphenous vein, heart right ventricle, blood vessel layer
CBR4	291	ubiquitous	marker	secondary oocyte, calcaneal tendon, oocyte

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EGFR	18,421
KRAS	14,509
HIF1A	9,734
ERBB2	9,659
BRCA1	9,064
BRAF	7,394
SMAD4	7,320
BRCA2	4,839
RB1	4,374
IGF2	4,294

Intra-cohort edges

A	B	Sources
BRAF	BRCA2	biogrid_interaction
BRAF	EGFR	biogrid_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRCA1	BRCA2	string_interaction
EGFR	ERBB2	intact, string_interaction
ERBB2	KRAS	string_interaction

Structural data

PDB: 13 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
EGFR	P00533	388
BRAF	P15056	131
ERBB2	P04626	63
BRCA1	P38398	33
HIF1A	Q16665	25
RB1	P06400	19
IGF2	P01344	16
BRCA2	P51587	14
SMAD4	Q13485	12
SLC29A1	Q99808	3
PALLD	Q8WX93	2
CBR4	Q8N4T8	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 283. Enrichment computed across 13 evidence-associated genes (12 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 12 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 ECD mutants	3	167.9×	1e-04	EGFR, ERBB2, KRAS
GRB2 events in ERBB2 signaling	3	158.6×	1e-04	EGFR, ERBB2, KRAS
SHC1 events in ERBB2 signaling	3	119.0×	1e-04	EGFR, ERBB2, KRAS
Signaling by ERBB2 TMD/JMD mutants	3	119.0×	1e-04	EGFR, ERBB2, KRAS
Signaling by ERBB2 KD Mutants	3	105.7×	1e-04	EGFR, ERBB2, KRAS
PLCG1 events in ERBB2 signaling	2	475.8×	3e-04	EGFR, ERBB2
PTK6 promotes HIF1A stabilization	2	271.9×	9e-04	EGFR, HIF1A
RAF/MAP kinase cascade	4	20.4×	0.001	BRAF, EGFR, ERBB2, KRAS
EGFR Transactivation by Gastrin	2	190.3×	0.001	EGFR, KRAS
SHC-related events triggered by IGF1R	2	190.3×	0.001	IGF2, KRAS
Constitutive Signaling by Overexpressed ERBB2	2	158.6×	0.002	ERBB2, KRAS
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2	158.6×	0.002	BRCA1, BRCA2
ERBB2 Activates PTK6 Signaling	2	135.9×	0.002	EGFR, ERBB2
Diseases of DNA Double-Strand Break Repair	2	135.9×	0.002	BRCA1, BRCA2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2	135.9×	0.002	BRCA1, BRCA2
GRB2 events in EGFR signaling	2	126.9×	0.002	EGFR, KRAS
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	2	126.9×	0.002	EGFR, ERBB2
SHC1 events in EGFR signaling	2	119.0×	0.002	EGFR, KRAS
Constitutive Signaling by EGFRvIII	2	119.0×	0.002	EGFR, KRAS
ERBB2 Regulates Cell Motility	2	119.0×	0.002	EGFR, ERBB2
PI3K events in ERBB2 signaling	2	112.0×	0.002	EGFR, ERBB2
Resolution of D-Loop Structures	2	105.7×	0.002	BRCA1, BRCA2
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	2	95.2×	0.002	EGFR, KRAS
Diseases of DNA repair	2	95.2×	0.002	BRCA1, BRCA2
Developmental Lineage of Mammary Gland Myoepithelial Cells	2	90.6×	0.002	EGFR, ERBB2
Impaired BRCA2 binding to PALB2	2	76.1×	0.003	BRCA1, BRCA2
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	70.5×	0.003	BRCA1, BRCA2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	70.5×	0.003	BRCA1, BRCA2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	70.5×	0.003	BRCA1, BRCA2
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	65.6×	0.004	BRCA1, BRCA2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
striated muscle cell differentiation	3	228.8×	1e-04	IGF2, KRAS, RB1
embryonic placenta development	3	176.8×	1e-04	EGFR, HIF1A, IGF2
regulation of transforming growth factor beta2 production	2	648.1×	5e-04	HIF1A, SMAD4
visual learning	3	70.7×	9e-04	BRAF, HIF1A, KRAS
positive regulation of miRNA transcription	3	67.0×	9e-04	EGFR, HIF1A, SMAD4
positive regulation of gene expression	5	14.9×	9e-04	BRAF, BRCA1, HIF1A, KRAS, SMAD4
epidermal growth factor receptor signaling pathway	3	57.2×	0.001	BRAF, EGFR, ERBB2
ERBB2-EGFR signaling pathway	2	259.3×	0.001	EGFR, ERBB2
regulation of DNA-templated transcription	5	12.1×	0.002	BRCA2, HIF1A, IGF2, SMAD4, RB1
neuron apoptotic process	3	42.7×	0.002	HIF1A, KRAS, RB1
regulation of DNA damage checkpoint	2	172.8×	0.002	BRCA1, BRCA2
digestive tract morphogenesis	2	152.5×	0.003	EGFR, HIF1A
glial cell proliferation	2	136.4×	0.003	KRAS, RB1
negative regulation of cell growth	3	33.2×	0.003	BRCA1, SMAD4, RB1
positive regulation of transcription by RNA polymerase II	6	6.9×	0.003	BRCA1, EGFR, HIF1A, IGF2, SMAD4, RB1
positive regulation of peptidyl-serine phosphorylation	2	117.8×	0.003	BRAF, EGFR
positive regulation of vascular endothelial growth factor production	2	76.2×	0.008	BRCA1, HIF1A
lactation	2	64.8×	0.010	SLC29A1, HIF1A
cellular response to ionizing radiation	2	63.2×	0.010	BRCA1, BRCA2
obsolete positive regulation of cell proliferation involved in heart valve morphogenesis	1	1296.3×	0.010	SMAD4
response to mineralocorticoid	1	1296.3×	0.010	KRAS
female gonad morphogenesis	1	1296.3×	0.010	SMAD4
negative regulation of cardiocyte differentiation	1	1296.3×	0.010	EGFR
negative regulation of cardiac myofibril assembly	1	1296.3×	0.010	SMAD4
negative regulation of protein catabolic process	2	56.4×	0.010	EGFR, SMAD4
positive regulation of DNA repair	2	55.2×	0.010	BRCA1, EGFR
fatty acid biosynthetic process	2	54.0×	0.010	BRCA1, CBR4
skeletal muscle cell differentiation	2	52.9×	0.010	KRAS, RB1
ERK1 and ERK2 cascade	2	48.9×	0.010	BRAF, SMAD4
cellular response to epidermal growth factor stimulus	2	48.9×	0.010	EGFR, ERBB2

Therapeutics

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 8 · Undrugged: 5

Druggability breadth: 10 of 13 evidence-associated genes (77%) 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
BRCA1	RIBOFLAVIN
SLC29A1	RIMONABANT
EGFR	LEVODOPA
ERBB2	CLOTRIMAZOLE
HIF1A	EMETINE
KRAS	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HIF1A	255	4
EGFR	175	4
ERBB2	83	4
SLC29A1	65	4
BRAF	48	4
BRCA1	12	4
KRAS	11	4
RB1	1	2
BRCA2	0	0
IGF2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF, EGFR, KRAS
PONATINIB	4	BRAF, EGFR, ERBB2
FEDRATINIB	4	BRAF, EGFR
SORAFENIB	4	BRAF, EGFR, ERBB2
DASATINIB ANHYDROUS	4	BRAF, EGFR
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, SLC29A1
ABEMACICLIB	4	BRAF, EGFR
ENCORAFENIB	4	BRAF, SLC29A1
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF, EGFR, ERBB2
ERLOTINIB	4	BRAF, EGFR, ERBB2, SLC29A1
GEFITINIB	4	BRAF, EGFR, ERBB2
IMATINIB	4	BRAF, EGFR, ERBB2
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1, HIF1A
TOPOTECAN HYDROCHLORIDE	4	BRCA1, HIF1A
DAUNORUBICIN	4	BRCA1, SLC29A1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1, HIF1A
MESALAMINE	4	BRCA1, HIF1A
DIPYRIDAMOLE	4	BRCA1, HIF1A, SLC29A1
RIMONABANT	4	SLC29A1
CELECOXIB	4	SLC29A1
BENZTROPINE	4	SLC29A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
KRAS	861	Binding:829, Functional:32
HIF1A	427	Binding:411, Functional:16
RB1	59	Binding:59
SLC29A1	49	Binding:38, ADMET:9, Functional:2
BRCA1	13	Binding:9, Functional:4
SMAD4	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
EGFR	2.7.10.1	receptor protein-tyrosine 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
BRAF	1,442
EGFR	6,531
ERBB2	1,221
HIF1A	427
KRAS	861

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

27 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	BRAF, EGFR, KRAS
PONATINIB	4	BRAF, EGFR, ERBB2
FEDRATINIB	4	BRAF, EGFR
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF, KRAS
NILOTINIB	4	BRAF, SLC29A1
ABEMACICLIB	4	BRAF, EGFR
ENCORAFENIB	4	BRAF, SLC29A1
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF, EGFR, ERBB2
ERLOTINIB	4	BRAF, EGFR, ERBB2, SLC29A1
GEFITINIB	4	BRAF, EGFR, ERBB2
IMATINIB	4	BRAF, EGFR, ERBB2
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1, HIF1A
TOPOTECAN HYDROCHLORIDE	4	BRCA1, HIF1A
DAUNORUBICIN	4	BRCA1, SLC29A1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1, HIF1A
MESALAMINE	4	BRCA1, HIF1A
DIPYRIDAMOLE	4	BRCA1, HIF1A, SLC29A1
RIMONABANT	4	SLC29A1
CELECOXIB	4	SLC29A1
BENZTROPINE	4	SLC29A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	BRAF, BRCA1, SLC29A1, EGFR, ERBB2, HIF1A, KRAS
B	Phased (≥1) drug, not yet approved	1	RB1
C	Druggable family + PDB, no drug	1	PALLD
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	BRCA2, IGF2, SMAD4, CBR4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
IGF2	0	—
SMAD4	6	—
PALLD	0	—
CBR4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 584.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	164
Not specified	158
PHASE1	131
PHASE1/PHASE2	83
PHASE3	30
EARLY_PHASE1	8
PHASE4	5
PHASE2/PHASE3	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07262957	PHASE4	RECRUITING	Preventing Postoperative Complications in Patients Undergoing High-risk Pancreatoduodenectomy With a Bundle Approach Including Hydrocortisone, Octreotide, and the Teres Ligament Patch (PANENCA)
NCT00854477	PHASE4	COMPLETED	Pharmacokinetic Study of Adjuvant Capecitabine After Resection of Pancreatic Adenocarcinoma
NCT01401387	PHASE4	WITHDRAWN	Pancreatic Enzyme Suppletion in Pancreatic Cancer
NCT02812992	PHASE4	COMPLETED	Geriatric Assessment Directed Trial to Evaluate Gemcitabine +/- Nab-paclitaxel in Elderly Pancreatic Cancer Patients
NCT03401827	PHASE4	UNKNOWN	The Effect of Gemcitabine Plus Nab-paclitaxel as Secondary Chemotherapy in Advanced Pancreatic Cancer
NCT01954992	PHASE3	RECRUITING	Glufosfamide Versus 5-FU in Second Line Metastatic Pancreatic Cancer
NCT05268692	PHASE2/PHASE3	RECRUITING	Neoadjuvant Chemotherapy for Pancreatic Cancer Followed by GS and GnP
NCT05482516	PHASE3	RECRUITING	Evaluating Novel Therapies in ctDNA Positive GI Cancers
NCT06018883	PHASE3	ACTIVE_NOT_RECRUITING	Vitamin C to Chemotherapy Related Anemia in Pancreatic Cancer
NCT06095141	PHASE2/PHASE3	RECRUITING	Cisplatin to Patients With Pancreatic Cancer and Homologous Recombination Deficiency
NCT06115499	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	The PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer
NCT06250972	PHASE3	RECRUITING	Radiotherapy to Patients With CA19-9-elevated Advanced Pancreatic Cancer
NCT06714604	PHASE3	RECRUITING	Standard or Prolonged Neoadjuvant Chemotherapy Before Surgery for BR/LAPC
NCT06861088	PHASE3	RECRUITING	The Effect of Kinisoquin™ on Thromboembolic Events in Patients With Metastatic or Locally Advanced Pancreatic Cancer
NCT06998940	PHASE3	RECRUITING	Studying Chemotherapy With or Without Panitumumab for Unresectable, Locally Advanced, or Metastatic Pancreatic Cancer Without KRAS Mutations
NCT07081360	PHASE3	RECRUITING	Neoadjuvant vs Upfront Surgery for Resectable Pancreatic Cancer and Periampullary Cancer
NCT07409272	PHASE3	RECRUITING	A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer
NCT07491445	PHASE3	RECRUITING	Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
NCT07562152	PHASE3	RECRUITING	Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
NCT00088894	PHASE3	COMPLETED	Gemcitabine With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
NCT01013649	PHASE3	COMPLETED	Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed by the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed by Surgery
NCT01231347	PHASE3	COMPLETED	QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas
NCT01360853	PHASE3	COMPLETED	Gemcitabine and ON 01910.Na in Previously Untreated Metastatic Pancreatic Cancer
NCT01419002	PHASE3	TERMINATED	Study to Evaluate if Neoadjuvant Radiotherapy Improves Recurrence Free Survival in Pancreatic Head Cancer
NCT01526135	PHASE3	COMPLETED	Trial Comparing Adjuvant Chemotherapy With Gemcitabine Versus mFolfirinox to Treat Resected Pancreatic Adenocarcinoma
NCT02184195	PHASE3	COMPLETED	Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy
NCT02436668	PHASE3	COMPLETED	Study of Ibrutinib vs Placebo, in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma (RESOLVE)
NCT03126435	PHASE3	COMPLETED	EndoTAG-1+GEM vs GEM in Patients With Locally Advanced/Metastatic Pancreatic Adenocarcinoma Failed on FOLFIRINOX
NCT03377491	PHASE3	COMPLETED	Effect of Tumor Treating Fields (TTFields, 150 kHz) as Front-Line Treatment of Locally-advanced Pancreatic Adenocarcinoma Concomitant With Gemcitabine and Nab-paclitaxel (PANOVA-3)
NCT03536182	PHASE3	WITHDRAWN	Trial of Carbon Ion Versus Photon Radiotherapy for Locally Advanced, Unresectable Pancreatic Cancer
NCT03649035	PHASE3	WITHDRAWN	Eus-guided Cryothermal Ablation in Stage III Pancreatic Adenocarcinoma
NCT03665441	PHASE3	COMPLETED	Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC
NCT03673137	PHASE2/PHASE3	COMPLETED	Phase II/III of Randomized Controlled Clinical Research on IRE Synchronous Chemotherapy for LAPC
NCT03943667	PHASE3	COMPLETED	Gemcitabine and Paclitaxel vs Gemcitabine Alone After FOLFIRINOX Failure in Metastatic Pancreatic Ductal Adenocarcinoma
NCT04083235	PHASE3	COMPLETED	A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment
NCT04167007	PHASE3	UNKNOWN	FOLFOX vs Gemcitabine in Patients With Metastatic Pancreatic Cancer Non-fit to FOLFIRINOX
NCT04229004	PHASE3	COMPLETED	A Multi-center Trial to Evaluate Multiple Regimens in Metastatic Pancreatic Cancer
NCT04617821	PHASE3	UNKNOWN	AG vs mFOLFIRINOX as Neoadjuvant Therapy for Borderline Reseactable and Locally Advanced Pancreatic Cancer
NCT04835064	PHASE3	UNKNOWN	Pancreatic Cancer With Elevated Serum CA125 Were Compared With Those Who Did Not Receive Neoadjuvant Chemotherapy.
NCT05181605	PHASE2/PHASE3	UNKNOWN	Survival Analysis After Neoadjuvant Therapy in Patients With Resectable Pancreatic Cancer and Risk Factors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CAPECITABINE	4	21
GEMCITABINE	4	4
PARICALCITOL	4	4
COBIMETINIB	4	3
OLAPARIB	4	3
SORAFENIB	4	3
TOCILIZUMAB	4	3
CERITINIB	4	2
DASATINIB ANHYDROUS	4	2
ERLOTINIB HYDROCHLORIDE	4	2
NELFINAVIR MESYLATE	4	2
NIRAPARIB	4	2
PANCRELIPASE	4	2
RETIFANLIMAB	4	2
VISMODEGIB	4	2
ZOLBETUXIMAB	4	2
BEVACIZUMAB	4	1
BINIMETINIB	4	1
CABOZANTINIB	4	1
CEMIPLIMAB	4	1
DIGOXIN	4	1
DISULFIRAM	4	1
DOSTARLIMAB	4	1
ENFORTUMAB VEDOTIN	4	1
ENTRECTINIB	4	1
ERIBULIN MESYLATE	4	1
ETHIODIZED OIL	4	1
FLOXURIDINE	4	1
FLUDEOXYGLUCOSE F 18	4	1
HYDROCORTISONE	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 19 predictive associations from 19 curated evidence items; also 2 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
BRCA1 Loss-of-function	Olaparib	Sensitivity/Response	CIViC A	EID7384
BRCA2 Loss-of-function	Olaparib	Sensitivity/Response	CIViC A	EID7385
NRG1 Fusion	Zenocutuzumab-zbco	Sensitivity/Response	CIViC A	EID12247
BRCA1 Mutation OR BRCA2 Mutation OR PALB2 Mutation	Rucaparib	Sensitivity/Response	CIViC B	EID11317
IGF2 Overexpression	Ganitumab + Gemcitabine	Sensitivity/Response	CIViC B	EID7000
KRAS G12/G13	Trametinib	Sensitivity/Response	CIViC B	EID990
SLC29A1 Overexpression	Gemcitabine	Sensitivity/Response	CIViC B	EID10145
KRAS G12/G13	Trametinib + Gemcitabine	Resistance	CIViC B	EID622
BRAF V600E	Dabrafenib/Trametinib Regimen	Sensitivity/Response	CIViC C	EID12811
EGFR L747_P753delinsS	Erlotinib	Sensitivity/Response	CIViC C	EID6005
EGFR T790M	Osimertinib	Sensitivity/Response	CIViC C	EID6006
NRG1 Fusion	Afatinib	Sensitivity/Response	CIViC C	EID6273
NRG1 Fusion	Erlotinib + Pertuzumab	Sensitivity/Response	CIViC C	EID7534
SLC4A4::ROS1 Fusion	Crizotinib	Sensitivity/Response	CIViC C	EID11651
MAP2K2 G132D	Trametinib	Resistance	CIViC C	EID7732
MAP2K2 G132S	Trametinib	Resistance	CIViC C	EID7733
ERBB2 Amplification	Afatinib	Sensitivity/Response	CIViC D	EID962
KRAS Mutation	SCH772984 + PI3Kbeta Inhibitor AZD8186	Sensitivity/Response	CIViC D	EID1003
RB1 Overexpression	Doxorubicin + Fluorouracil + Gemcitabine + Mitomycin	Resistance	CIViC D	EID1324