Gallbladder cancer

Summary

Gallbladder cancer (MONDO:0005411) is a cancer (an umbrella term covering 5 Mondo subtypes) with 6 cohort genes (6 CIViC-evidence somatic drivers; 13 ClinVar predisposition records) and 189 clinical trials. Top therapeutic interventions include gemcitabine hydrochloride, lapatinib, and porfimer sodium.

At a glance

• Classification: Cancer
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 6
• ClinVar variants: 13
• Clinical trials: 189

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gallbladder cancer
Mondo ID	MONDO:0005411
DOID	DOID:3121
ICD-10-CM	C23
ICD-11	922082116
NCIT	C7481
SNOMED CT	363353009
UMLS	C0153452
MedGen	57784
GARD	0009328
Anatomy (UBERON)	UBERON:0002110
Is cancer (heuristic)	yes

Also known as: cancer of gall bladder · gall bladder cancer · gallbladder neoplasm · localised malignant gallbladder neoplasm · localized malignant gallbladder neoplasm · malignant gall bladder neoplasm · malignant gallbladder neoplasm · malignant gallbladder tumor · malignant gallbladder tumour · malignant neoplasm of gall bladder · malignant neoplasm of gallbladder · malignant neoplasm of the gallbladder · malignant tumor of gallbladder · malignant tumor of the gallbladder · malignant tumour of gallbladder · malignant tumour of the gallbladder · tumor of the gallbladder · tumour of the gallbladder

Data availability: 13 ClinVar variants · 10 intOGen driver records.

Disease family

An umbrella term covering 5 Mondo subtypes.

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

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

Subtypes (5): gallbladder sarcoma, gallbladder carcinoma, neurofibroma of gallbladder, gallbladder lymphoma, gallbladder melanoma

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

13 retrieved; paginated sample, class counts are floors:

5 pathogenic/likely pathogenic, 4 pathogenic, 2 likely pathogenic, 1 uncertain significance, 1 pathogenic; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
17588	NM_001904.4(CTNNB1):c.134C>T (p.Ser45Phe)	CTNNB1	Pathogenic; other	no assertion criteria provided
45122	NM_004985.5(KRAS):c.35G>C (p.Gly12Ala)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13655	NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys)	PIK3CA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
24850	NM_005359.6(SMAD4):c.1333C>T (p.Arg445Ter)	SMAD4	Pathogenic	criteria provided, multiple submitters, no conflicts
12347	NM_000546.6(TP53):c.742C>T (p.Arg248Trp)	TP53	Pathogenic	reviewed by expert panel
182935	NM_000546.6(TP53):c.713G>A (p.Cys238Tyr)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182970	NM_000546.6(TP53):c.1024C>T (p.Arg342Ter)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
186236	NM_000546.6(TP53):c.376-2A>G	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
232497	NM_000546.6(TP53):c.833C>T (p.Pro278Leu)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
376588	NM_000546.6(TP53):c.841G>C (p.Asp281His)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375948	NM_004333.6(BRAF):c.1779_1780delinsGA (p.Asp594Asn)	BRAF	Likely pathogenic	no assertion criteria provided
12578	NM_004985.5(KRAS):c.34G>T (p.Gly12Cys)	KRAS	Likely pathogenic	criteria provided, single submitter
1064425	NM_004333.6(BRAF):c.1759G>A (p.Asp587Asn)	BRAF	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 74 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
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
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
CTNNB1	Act	ACC,COAD,COADREAD,ESCA,HCC,LIHB,LUAD,MBL,MEL,NSCLC,OVT,PAST,PRAD,PROSTATE,RMS,SKIN,SOFT_TISSUE,STAD,UCEC,WT	CIViC #1290
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
SMAD4	LoF	BRCA,CESC,CHOL,COAD,COADREAD,ESCA,ESCC,GBC,HNSC,LUAD,NSCLC,PAAD,PANCREAS,PRAD,PROSTATE,READ,STAD,STOMACH	CIViC #77
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37

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
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
CTNNB1	Orphanet:1501	Adrenocortical carcinoma
CTNNB1	Orphanet:210159	Adult hepatocellular carcinoma
CTNNB1	Orphanet:2780	Osteopathia striata-cranial sclerosis syndrome
CTNNB1	Orphanet:33402	Pediatric hepatocellular carcinoma
CTNNB1	Orphanet:404473	Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome
CTNNB1	Orphanet:54595	Craniopharyngioma
CTNNB1	Orphanet:569248	Microcystic stromal tumor
CTNNB1	Orphanet:689430	Adenoid ameloblastoma
CTNNB1	Orphanet:873	Desmoid tumor
CTNNB1	Orphanet:891	Familial exudative vitreoretinopathy
CTNNB1	Orphanet:91414	Pilomatrixoma
CTNNB1	Orphanet:952	Acrofacial dysostosis, Weyers type
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

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	clinvar
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar
SMAD4	HGNC:6770	ENSG00000141646	Q13485	SMAD family member 4	clinvar
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	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.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.
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.
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.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.5

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	2	9.2×	0.071
Enzyme (other)	1	2.0×	0.719
Transcription factor	1	1.4×	0.719
Other/Unknown	2	0.6×	0.936

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
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin
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
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	3
ventricular zone	3
ganglionic eminence	2
adrenal tissue	2
buccal mucosa cell	1
colonic epithelium	1
tendon of biceps brachii	1
periodontal ligament	1
nipple	1
pylorus	1
trigeminal ganglion	1
tendon	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
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
SMAD4	288	ubiquitous	marker	ventricular zone, ganglionic eminence, calcaneal tendon
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
CTNNB1	15,668
KRAS	14,509
BRAF	7,394
SMAD4	7,320
PIK3CA	5,157

Intra-cohort edges

A	B	Sources
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	TP53	string_interaction
CTNNB1	SMAD4	string_interaction
KRAS	PIK3CA	string_interaction
KRAS	TP53	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
PIK3CA	P42336	135
BRAF	P15056	131
CTNNB1	P35222	50
SMAD4	Q13485	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 269. Enrichment computed across 6 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX3 regulates CDKN1A transcription	2	543.8×	9e-04	TP53, SMAD4
Signaling by FGFR4 in disease	2	317.2×	9e-04	KRAS, PIK3CA
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	2	292.8×	9e-04	KRAS, PIK3CA
Signaling by PDGFRA extracellular domain mutants	2	292.8×	9e-04	KRAS, PIK3CA
Signaling by FLT3 ITD and TKD mutants	2	253.8×	9e-04	KRAS, PIK3CA
Constitutive Signaling by EGFRvIII	2	237.9×	9e-04	KRAS, PIK3CA
Formation of definitive endoderm	2	237.9×	9e-04	CTNNB1, SMAD4
Signaling by ERBB2 ECD mutants	2	223.9×	9e-04	KRAS, PIK3CA
Germ layer formation at gastrulation	2	223.9×	9e-04	CTNNB1, SMAD4
Tie2 Signaling	2	200.3×	1e-03	KRAS, PIK3CA
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	2	190.3×	1e-03	KRAS, PIK3CA
Signaling by FLT3 fusion proteins	2	190.3×	1e-03	KRAS, PIK3CA
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	2	173.0×	0.001	KRAS, PIK3CA
Signaling by FGFR3 in disease	2	165.5×	0.001	KRAS, PIK3CA
Signaling by ERBB2 KD Mutants	2	141.0×	0.001	KRAS, PIK3CA
Cardiogenesis	2	141.0×	0.001	CTNNB1, SMAD4
RAF/MAP kinase cascade	3	30.5×	0.001	BRAF, KRAS, PIK3CA
Downstream signal transduction	2	126.9×	0.001	KRAS, PIK3CA
DAP12 signaling	2	122.8×	0.002	KRAS, PIK3CA
FLT3 Signaling	2	115.3×	0.002	KRAS, PIK3CA
Signaling by CSF1 (M-CSF) in myeloid cells	2	115.3×	0.002	KRAS, PIK3CA
RAF activation	2	112.0×	0.002	BRAF, KRAS
Signaling by high-kinase activity BRAF mutants	2	105.7×	0.002	BRAF, KRAS
Signaling by FGFR1 in disease	2	97.6×	0.002	KRAS, PIK3CA
MAP2K and MAPK activation	2	95.2×	0.002	BRAF, KRAS
Signaling by RAF1 mutants	2	92.8×	0.002	BRAF, KRAS
Signaling by FGFR2 in disease	2	88.5×	0.002	KRAS, PIK3CA
Negative regulation of MAPK pathway	2	88.5×	0.002	BRAF, KRAS
Transcriptional Regulation by VENTX	2	88.5×	0.002	TP53, CTNNB1
Signaling by moderate kinase activity BRAF mutants	2	84.6×	0.002	BRAF, KRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of gene expression	5	32.3×	3e-05	BRAF, TP53, CTNNB1, KRAS, SMAD4
T cell differentiation in thymus	3	205.5×	6e-05	BRAF, TP53, CTNNB1
epidermal growth factor receptor signaling pathway	3	123.9×	2e-04	BRAF, CTNNB1, PIK3CA
MAPK cascade	3	76.6×	6e-04	BRAF, CTNNB1, KRAS
myoblast proliferation	2	468.1×	6e-04	CTNNB1, KRAS
positive regulation of cellular senescence	2	432.1×	6e-04	TP53, KRAS
positive regulation of cardiac muscle cell apoptotic process	2	401.2×	6e-04	TP53, SMAD4
negative regulation of neuron apoptotic process	3	55.4×	7e-04	BRAF, KRAS, PIK3CA
gastrulation with mouth forming second	2	312.1×	8e-04	CTNNB1, SMAD4
glial cell proliferation	2	295.6×	8e-04	TP53, KRAS
epithelial tube branching involved in lung morphogenesis	2	280.9×	8e-04	CTNNB1, KRAS
in utero embryonic development	3	36.0×	0.002	TP53, CTNNB1, SMAD4
branching involved in ureteric bud morphogenesis	2	122.1×	0.003	CTNNB1, SMAD4
neuroblast proliferation	2	122.1×	0.003	TP53, CTNNB1
thymus development	2	112.3×	0.003	BRAF, CTNNB1
positive regulation of epithelial to mesenchymal transition	2	106.0×	0.003	CTNNB1, SMAD4
ERK1 and ERK2 cascade	2	106.0×	0.003	BRAF, SMAD4
epithelial to mesenchymal transition	2	104.0×	0.003	CTNNB1, SMAD4
stem cell proliferation	2	104.0×	0.003	TP53, CTNNB1
visual learning	2	102.1×	0.003	BRAF, KRAS
embryonic digit morphogenesis	2	100.3×	0.003	CTNNB1, SMAD4
positive regulation of miRNA transcription	2	96.8×	0.003	TP53, SMAD4
positive regulation of neuron apoptotic process	2	90.6×	0.004	TP53, CTNNB1
cellular response to glucose stimulus	2	89.2×	0.004	SMAD4, PIK3CA
obsolete positive regulation of cell proliferation involved in heart valve morphogenesis	1	2808.7×	0.004	SMAD4
glial cell fate determination	1	2808.7×	0.004	CTNNB1
response to muscle inactivity	1	2808.7×	0.004	PIK3CA
canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation	1	2808.7×	0.004	CTNNB1
negative regulation of helicase activity	1	2808.7×	0.004	TP53
response to mineralocorticoid	1	2808.7×	0.004	KRAS

Therapeutics

Drug target analysis

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

Druggability breadth: 6 of 6 evidence-associated genes (100%) 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
TP53	NITROFURANTOIN
CTNNB1	DITHIAZANINE IODIDE
KRAS	VEMURAFENIB
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
PIK3CA	67	4
BRAF	48	4
KRAS	11	4
CTNNB1	4	4
SMAD4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF, PIK3CA
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF, PIK3CA
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
CTNNB1	361	Binding:358, Functional:3
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
KRAS	3.6.5.2	small monomeric GTPase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase

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
TP53	869
CTNNB1	361
KRAS	861
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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)
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF, PIK3CA
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF, KRAS
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF, PIK3CA
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	BRAF, TP53, CTNNB1, KRAS, PIK3CA
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SMAD4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SMAD4	6	CTNNB1

Clinical trials & evidence

Clinical trials

Clinical trials: 189.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	65
Not specified	63
PHASE1	29
PHASE3	12
PHASE2/PHASE3	9
PHASE1/PHASE2	9
PHASE4	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT02174575	PHASE4	WITHDRAWN	Anesthetic Agents and Acute Kidney Injury After Liver Resection Surgery
NCT02867865	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Perioperative Therapy Preoperative Chemotherapy Versus Chemoradiotherapy in Locally Advanced Gall Bladder Cancers
NCT04559139	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer
NCT05506943	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
NCT05786716	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With HER2 Amplification or Activating Mutations
NCT05833815	PHASE2/PHASE3	RECRUITING	Addition of Everolimus to Standard of Care in Carcinoma Gallbladder
NCT06214572	PHASE2/PHASE3	RECRUITING	Radiation Therapy in Unresectable Gall Bladder Cancer
NCT06671418	PHASE3	ENROLLING_BY_INVITATION	Primary Percutaneous Stenting Above the Ampulla Versus Endoscopic Drainage for Unresectable Malignant Hilar Biliary Obstruction
NCT00253617	PHASE3	WITHDRAWN	Stent Placement With or Without Photodynamic Therapy Using Porfimer Sodium as Palliative Treatment in Treating Patients With Stage III or Stage IV Cholangiocarcinoma That Cannot Be Removed By Surgery
NCT00262769	PHASE3	COMPLETED	Gemcitabine With or Without Cisplatin in Treating Patients With Unresectable Locally Advanced or Metastatic Cholangiocarcinoma or Other Biliary Tract Tumors
NCT00304135	PHASE2/PHASE3	COMPLETED	Fluorouracil, Cisplatin, and Radiation Therapy or Gemcitabine and Oxaliplatin in Treating Patients With Nonmetastatic Biliary Tract Cancer That Cannot Be Removed By Surgery
NCT00363584	PHASE3	COMPLETED	Capecitabine or Observation After Surgery in Treating Patients With Biliary Tract Cancer
NCT00387348	PHASE3	TERMINATED	Escitalopram in Treating Depression in Patients With Advanced Lung or Gastrointestinal Cancer
NCT00391183	PHASE2/PHASE3	COMPLETED	Palliative Biliary Stenting on the Quality of Life of Patients With Unresectable Carcinoma Gallbladder With Hiliar Block.
NCT00513539	PHASE3	COMPLETED	Biliary Stenting With or Without Photodynamic Therapy in Treating Patients With Locally Advanced, Recurrent, or Metastatic Cholangiocarcinoma or Other Biliary Tract Tumors That Cannot Be Removed by Surgery
NCT00658593	PHASE3	TERMINATED	Gemcitabine With/Out Capecitabine in Locally Advanced, Unresectable, or Metastatic Biliary Cancer
NCT01053390	PHASE3	COMPLETED	New Chemotherapy Regimen in the Treatment of Advanced Gallbladder Carcinoma
NCT01313377	PHASE3	COMPLETED	Gemcitabine Hydrochloride and Oxaliplatin or Observation in Treating Patients With Biliary Tract Cancer That Has Been Removed by Surgery
NCT01926236	PHASE3	COMPLETED	Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers
NCT03579758	PHASE3	WITHDRAWN	Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer
NCT03768414	PHASE3	COMPLETED	Gemcitabine Hydrochloride and Cisplatin With or Without Nab-Paclitaxel in Treating Patients With Newly Diagnosed Advanced Biliary Tract Cancers
NCT04066491	PHASE2/PHASE3	TERMINATED	Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC
NCT04068194	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies
NCT04308174	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Gemcitabine Plus Cisplatin With or Without Durvalumab in Resectable Biliary Tract Cancer
NCT04585750	PHASE1/PHASE2	RECRUITING	The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)
NCT04941287	PHASE2	ACTIVE_NOT_RECRUITING	Testing A New Combination of Anti-cancer Immune Therapies, Atezolizumab and CDX-1127 (Varlilumab) With or Without the Addition of a Third Anti-cancer Drug, Cobimetinib, for Advanced-Stage Biliary Tract Cancer
NCT05564403	PHASE2	ACTIVE_NOT_RECRUITING	Study of Chemotherapy, With or Without Binimetinib in Advanced Biliary Tract Cancers in 2nd Line Setting (A ComboMATCH Treatment Trial)
NCT05757336	PHASE2	RECRUITING	Combination of Gemcitabine, Albumin-paclitaxel , Sintilimab and Bevacizumab in Unresectable Gallbladder Cancer
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT06717464	PHASE2	ACTIVE_NOT_RECRUITING	Toripalimab Combined With Capecitabine as Postoperative Adjuvant Therapy for Patients With Resectable Advanced Extrahepatic Biliary Tract Cancer
NCT06852287	PHASE2	RECRUITING	Phase II Clinical Study of GemOX Hepatic Arterial Infusion Combined with Lenvatinib and Toripalimab for Advanced and Unresectable Intrahepatic Cholangiocarcinoma and Gallbladder Cancer
NCT06963060	PHASE2	ENROLLING_BY_INVITATION	Gem+Nab-P+LEN+TIS for Advanced Unresectable BTC (GALENT-BT)
NCT07025174	PHASE2	RECRUITING	Sequential Anti-Angiogenic Therapy After Immunotherapy in Advanced Biliary Tract Cancer
NCT07146646	PHASE2	RECRUITING	Trifluridine/Tipiracil + Oxaliplatin in Participants With Advanced or Metastatic Biliary Tract Cancer
NCT00003276	PHASE2	COMPLETED	Irinotecan in Treating Patients With Advanced Gallbladder or Bile Duct Cancer
NCT00003296	PHASE2	UNKNOWN	Liposomal Doxorubicin in Treating Patients With Liver or Bile Duct Cancer
NCT00003557	PHASE2	COMPLETED	Dolastatin 10 in Treating Patients With Metastatic Or Recurrent Liver, Bile Duct, or Gallbladder Cancer
NCT00003923	PHASE2	COMPLETED	Photodynamic Therapy in Treating Patients With Cancer of the Bile Duct, Gallbladder, or Pancreas
NCT00005938	PHASE2	COMPLETED	DX-8951f in Treating Patients With Biliary Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GEMCITABINE HYDROCHLORIDE	4	6
LAPATINIB	4	6
PORFIMER SODIUM	4	3
TIPIRACIL	4	3
TRIFLURIDINE	4	3
EPIRUBICIN	4	2
ERLOTINIB HYDROCHLORIDE	4	2
OXALIPLATIN	4	2
SELUMETINIB	4	2
TIVOZANIB	4	2
BINIMETINIB	4	1
CAPECITABINE	4	1
CITALOPRAM	4	1
COBIMETINIB	4	1
CRIZOTINIB	4	1
DESFLURANE	4	1
ESCITALOPRAM OXALATE	4	1
IXABEPILONE	4	1
LEVOLEUCOVORIN	4	1
PALONOSETRON HYDROCHLORIDE	4	1
PERTUZUMAB	4	1
RAMUCIRUMAB	4	1
SARGRAMOSTIM	4	1
SEVOFLURANE	4	1
SORAFENIB TOSYLATE	4	1
TORIPALIMAB	4	1
TRAMETINIB	4	1
VANDETANIB	4	1
BINTRAFUSP ALFA	3	2
EXATECAN	3	2