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Atlas / Disease / Biliary tract cancer

Biliary tract cancer

disease
On this page

Also known as biliary tree cancercancer of biliary treemalignant biliary tree neoplasmmalignant neoplasm of biliary treemalignant tumor of biliary tract

Summary

Biliary tract cancer (MONDO:0003060) is a cancer with 5 cohort genes (45 GWAS associations across 9 studies; 5 CIViC-evidence somatic drivers) and 294 clinical trials. Molecularly, BRAF V600E confers sensitivity to Dabrafenib + Trametinib in Biliary Tract Cancer (CIViC Level B); 4 further subtype–drug associations are mapped below. Top therapeutic interventions include oxaliplatin, durvalumab, and levoleucovorin.

At a glance

  • Classification: Cancer
  • Cohort genes: 5
  • GWAS associations: 45
  • Clinical trials: 294
  • Precision-medicine evidence (CIViC): 5 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namebiliary tract cancer
Mondo IDMONDO:0003060
DOIDDOID:4607
UMLSC0750952
MedGen155474
GARD0005924
Anatomy (UBERON)UBERON:0001173
Is cancer (heuristic)yes

Also known as: biliary tree cancer · cancer of biliary tree · malignant biliary tree neoplasm · malignant neoplasm of biliary tree · malignant tumor of biliary tract

Data availability: 45 GWAS associations (9 studies).

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › digestive system cancer › liver cancer › biliary tract cancer

Related subtypes (4): liver sarcoma, liver lymphoma, calcifying nested epithelial stromal tumor of the liver, carcinoma of liver and intrahepatic biliary tract

Subtypes (2): bile duct cancer, biliary cystadenocarcinoma

Genetics & variants

GWAS landscape

45 GWAS associations across 9 studies. Top hits map to 30 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs126823749e-29PCAT1, CASC8, POU5F1B?0.93
rs12196511e-25FGFR2?1.09
rs29815841e-21FGFR2?0.94
rs109082783e-21HNF1B?1.06
rs1121495732e-17TOX3?1.08
rs785405261e-15LINC01488 - PNCRNA-D?1.13
rs354097102e-15HLA-DQB1?1.09
rs74637082e-15PCAT1, PRNCR1, CASC19?1.08
rs116517551e-14HNF1B?1.06
rs14859958e-14LINC01488?0.95
rs92737362e-13HLA-DQB1?1.12
rs29763843e-13PSCA, JRK?1.07
rs25851813e-12PSCA - LY6K?1.05
rs40076426e-11CDKN2B-AS1?0.96
rs107867741e-10STN1?0.92
rs29902231e-10GBA1LP, GBA1LP?1.09
rs44429752e-10TESHL?0.96
rs46302402e-10RPL23AP61?0.96
rs18599638e-10CASC17?0.96
rs118132688e-10STN1 - SLK?1.05
rs108912462e-09POU2AF3, COLCA1?0.96
rs18273368452e-09CHCHD4P2 - RPL36P14?1.05
rs69135783e-09CCDC170 - ESR1?1.04
rs25255483e-09Y_RNA - AZGP1?0.96
rs2057803e-09LINC-PINT?1.05
rs22378965e-09KCNQ1?1.05
rs7781886827e-09C5orf67 - MAP3K1?1.07
rs48485999e-09LINC01101 - Y_RNA?1.05
rs8308881e-08PELO-AS1?1.07
rs11052911e-08RCCD1?0.96

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90651054Sato G202343,098334,343Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90308764Sato G202329,753150,462Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651069Sato G202329,753150,462Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651040Sato G2023525334,343Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90013694Ishigaki K2020339195,745Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST90308750Sato G2023232150,462Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651055Sato G2023232150,462Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90013736Ishigaki K202021197,655Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST90013771Ishigaki K202012898,090Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory1
Tier 4: intronic/intergenic39

MAF distribution

BucketVariants
common (>=0.05)37
low_freq (0.01-0.05)0
rare (<0.01)0
unknown3

Functional consequences

ConsequenceCount
intron_variant28
intergenic_variant8
non_coding_transcript_exon_variant3
regulatory_region_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs126823748127398703C>A,G,T0.05intron_variantPCAT1, CASC8, POU5F1B9e-29Tier 4: intronic/intergenic
rs121965110121584987G>A,C,T0.05intron_variantFGFR21e-25Tier 4: intronic/intergenic
rs298158410121590702A>C,G,T0.05intron_variantFGFR21e-21Tier 4: intronic/intergenic
rs109082781737739961A>C,G,T0.05intron_variantHNF1B3e-21Tier 4: intronic/intergenic
rs1121495731652547333G>C,T0.05intron_variantTOX32e-17Tier 4: intronic/intergenic
rs785405261169516650C>T0.05regulatory_region_variantLINC01488 - PNCRNA-D1e-15Tier 3: regulatory
rs35409710632661126G>A0.05intron_variantHLA-DQB12e-15Tier 4: intronic/intergenic
rs74637088127091810G>A,C,T0.05non_coding_transcript_exon_variantPCAT1, PRNCR1, CASC192e-15Tier 4: intronic/intergenic
rs116517551737739849T>C0.05intron_variantHNF1B1e-14Tier 4: intronic/intergenic
rs14859951169492939G>A,C0.05non_coding_transcript_exon_variantLINC014888e-14Tier 4: intronic/intergenic
rs9273736632661595G>A,C0.05intron_variantHLA-DQB12e-13Tier 4: intronic/intergenic
rs29763848142671576T>A,C0.05intergenic_variantPSCA, JRK3e-13Tier 4: intronic/intergenic
rs25851818142690296C>A0.05intergenic_variantPSCA - LY6K3e-12Tier 4: intronic/intergenic
rs4007642922093300A>C,T0.05intron_variantCDKN2B-AS16e-11Tier 4: intronic/intergenic
rs1078677410103884565G>A,C,T0.05intron_variantSTN11e-10Tier 4: intronic/intergenic
rs29902231155215184G>A,T0.05intron_variantGBA1LP, GBA1LP1e-10Tier 4: intronic/intergenic
rs44429752217056046G>A,C,T0.05intron_variantTESHL2e-10Tier 4: intronic/intergenic
rs46302401046063294C>A,T0.05non_coding_transcript_exon_variantRPL23AP612e-10Tier 4: intronic/intergenic
rs18599631771116966T>A,C0.05intron_variantCASC178e-10Tier 4: intronic/intergenic
rs1181326810103922538C>T0.05intron_variantSTN1 - SLK8e-10Tier 4: intronic/intergenic
rs1089124611111299815A>G,T0.05intron_variantPOU2AF3, COLCA12e-09Tier 4: intronic/intergenic
rs18273368459108131440GGTATT>Gintergenic_variantCHCHD4P2 - RPL36P142e-09Tier 4: intronic/intergenic
rs69135786151628671A>C,T0.05intergenic_variantCCDC170 - ESR13e-09Tier 4: intronic/intergenic
rs2525548799955544C>A,G,T0.05intergenic_variantY_RNA - AZGP13e-09Tier 4: intronic/intergenic
rs2057807130966100G>A0.05intron_variantLINC-PINT3e-09Tier 4: intronic/intergenic
rs2237896112837210G>A,T0.05intron_variantKCNQ15e-09Tier 4: intronic/intergenic
rs778188682556757919intergenic_variantC5orf67 - MAP3K17e-09Tier 4: intronic/intergenic
rs48485992120481784T>A,C,G0.05intergenic_variantLINC01101 - Y_RNA9e-09Tier 4: intronic/intergenic
rs830888552727882T>A,C0.05intron_variantPELO-AS11e-08Tier 4: intronic/intergenic
rs11052911590959153C>A,G,T0.05intron_variantRCCD11e-08Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 44 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
BRAFActBLCA,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,WDTCCIViC #5
BRCA1LoFBLCA,BRCA,MEL,OVTCIViC #6
BRCA2LoFBLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVACIViC #7
CDKN2ALoFACYC,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,WDTCCIViC #14
ERBB2ActBLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCECCIViC #20

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BRAFOrphanet:1340Cardiofaciocutaneous syndrome
BRAFOrphanet:146Differentiated thyroid carcinoma
BRAFOrphanet:251615Pilomyxoid astrocytoma
BRAFOrphanet:389Langerhans cell histiocytosis
BRAFOrphanet:500Noonan syndrome with multiple lentigines
BRAFOrphanet:54595Craniopharyngioma
BRAFOrphanet:58017Classic hairy cell leukemia
BRAFOrphanet:626Large/giant congenital melanocytic nevus
BRAFOrphanet:648Noonan syndrome
BRAFOrphanet:840Syringocystadenoma papilliferum
BRAFOrphanet:96253Cushing disease
BRCA1Orphanet:1331Familial prostate cancer
BRCA1Orphanet:1333Familial pancreatic carcinoma
BRCA1Orphanet:145Hereditary breast and/or ovarian cancer syndrome
BRCA1Orphanet:168829Primary peritoneal carcinoma
BRCA1Orphanet:227535Hereditary breast cancer
BRCA1Orphanet:667662Breast implant-associated anaplastic large cell lymphoma
BRCA1Orphanet:694963Inflammatory breast cancer
BRCA1Orphanet:70567Cholangiocarcinoma
BRCA1Orphanet:84Fanconi anemia
BRCA2Orphanet:1331Familial prostate cancer
BRCA2Orphanet:1333Familial pancreatic carcinoma
BRCA2Orphanet:145Hereditary breast and/or ovarian cancer syndrome
BRCA2Orphanet:178Chordoma
BRCA2Orphanet:227535Hereditary breast cancer
BRCA2Orphanet:319462Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2Orphanet:440437Familial colorectal cancer Type X
BRCA2Orphanet:654Nephroblastoma
BRCA2Orphanet:667662Breast implant-associated anaplastic large cell lymphoma
BRCA2Orphanet:694963Inflammatory breast cancer
BRCA2Orphanet:70567Cholangiocarcinoma
BRCA2Orphanet:84Fanconi anemia
CDKN2AOrphanet:1333Familial pancreatic carcinoma
CDKN2AOrphanet:1501Adrenocortical carcinoma
CDKN2AOrphanet:252206Melanoma and neural system tumor syndrome
CDKN2AOrphanet:404560Familial atypical multiple mole melanoma syndrome
CDKN2AOrphanet:524Li-Fraumeni syndrome
CDKN2AOrphanet:585909B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2AOrphanet:618Familial melanoma
CDKN2AOrphanet:99861Precursor T-cell acute lymphoblastic leukemia
ERBB2Orphanet:213726Serous carcinoma of the corpus uteri
ERBB2Orphanet:2800Extramammary Paget disease
ERBB2Orphanet:388Hirschsprung disease
ERBB2Orphanet:99976Adenocarcinoma of the oesophagus and oesophagogastric junction

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only5

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
BRAFHGNC:1097ENSG00000157764P15056Serine/threonine-protein kinase B-rafcivic_evidence
BRCA1HGNC:1100ENSG00000012048P38398Breast cancer type 1 susceptibility proteincivic_evidence
BRCA2HGNC:1101ENSG00000139618P51587Breast cancer type 2 susceptibility proteincivic_evidence
CDKN2AHGNC:1787ENSG00000147889P42771Cyclin-dependent kinase inhibitor 2Acivic_evidence
ERBB2HGNC:3430ENSG00000141736P04626Receptor tyrosine-protein kinase erbB-2civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
BRAFSerine/threonine-protein kinase B-rafProtein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
BRCA1Breast cancer type 1 susceptibility proteinE3 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.
BRCA2Breast cancer type 2 susceptibility proteinInvolved in double-strand break repair and/or homologous recombination.
CDKN2ACyclin-dependent kinase inhibitor 2AActs as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
ERBB2Receptor tyrosine-protein kinase erbB-2Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.4

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.

FamilyGenesFoldFDR
Kinase211.1×0.048
Scaffold/PPI13.5×0.515
Transcription factor11.6×0.634
Other/Unknown10.4×0.983

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
BRAFKinaseyes2.7.10.2Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
BRCA1Transcription factorno2.3.2.27BRCT_dom, Znf_RING, BRCA1
BRCA2Other/UnknownnoBRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
CDKN2AScaffold/PPInoAnkyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
ERBB2Kinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

5 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)5
unknown0

Top tissues across cohort

TissueCohort genes
male germ line stem cell (sensu Vertebrata) in testis2
ventricular zone2
buccal mucosa cell1
calcaneal tendon1
colonic epithelium1
primordial germ cell in gonad1
secondary oocyte1
cervix squamous epithelium1
parotid gland1
pituitary gland1
lower esophagus mucosa1
right uterine tube1
sural nerve1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
BRAF265ubiquitousmarkerbuccal mucosa cell, colonic epithelium, calcaneal tendon
BRCA1208ubiquitousmarkerventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2184ubiquitousmarkermale germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
CDKN2A220ubiquitousmarkerparotid gland, cervix squamous epithelium, pituitary gland
ERBB2276ubiquitousmarkerlower esophagus mucosa, right uterine tube, sural nerve

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

SymbolInteractor count
ERBB29,659
CDKN2A9,311
BRCA19,064
BRAF7,394
BRCA24,839

Intra-cohort edges

ABSources
BRAFBRCA2biogrid_interaction
BRAFCDKN2Astring_interaction
BRCA1BRCA2string_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
BRAFP15056131
ERBB2P0462663
BRCA1P3839833
BRCA2P5158714
CDKN2AP427715

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 170. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Defective homologous recombination repair (HRR) due to PALB2 loss of function2380.7×8e-04BRCA1, BRCA2
Diseases of DNA Double-Strand Break Repair2326.3×8e-04BRCA1, BRCA2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function2326.3×8e-04BRCA1, BRCA2
Resolution of D-Loop Structures2253.8×1e-03BRCA1, BRCA2
Diseases of DNA repair2228.4×1e-03BRCA1, BRCA2
Impaired BRCA2 binding to PALB22182.7×0.001BRCA1, BRCA2
Defective homologous recombination repair (HRR) due to BRCA1 loss of function2169.2×0.001BRCA1, BRCA2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function2169.2×0.001BRCA1, BRCA2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function2169.2×0.001BRCA1, BRCA2
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)2157.5×0.001BRCA1, BRCA2
Homologous DNA Pairing and Strand Exchange2152.3×0.001BRCA1, BRCA2
Homology Directed Repair2123.5×0.001BRCA1, BRCA2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)2123.5×0.001BRCA1, BRCA2
Impaired BRCA2 binding to RAD512123.5×0.001BRCA1, BRCA2
Resolution of D-loop Structures through Holliday Junction Intermediates2120.2×0.001BRCA1, BRCA2
Meiosis2114.2×0.001BRCA1, BRCA2
Presynaptic phase of homologous DNA pairing and strand exchange2108.8×0.001BRCA1, BRCA2
DNA Double-Strand Break Repair299.3×0.001BRCA1, BRCA2
Disease410.5×0.001BRAF, BRCA1, BRCA2, CDKN2A
Cell Cycle321.6×0.002BRCA1, BRCA2, CDKN2A
Reproduction276.1×0.002BRCA1, BRCA2
HDR through Homologous Recombination (HRR)276.1×0.002BRCA1, BRCA2
MITF-M-dependent gene expression272.5×0.002BRCA1, CDKN2A
SUMO E3 ligases SUMOylate target proteins271.4×0.002BRCA1, CDKN2A
SUMOylation265.3×0.002BRCA1, CDKN2A
Evasion of Oncogene Induced Senescence Due to p14ARF Defects12284.0×0.003CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects12284.0×0.003CDKN2A
SUMOylation of DNA damage response and repair proteins258.6×0.003BRCA1, CDKN2A
Cellular response to chemical stress257.1×0.003BRCA1, CDKN2A
Regulation of TP53 Activity253.1×0.003BRCA1, CDKN2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
negative regulation of mammary gland epithelial cell proliferation21348.2×1e-04BRCA2, CDKN2A
negative regulation of immature T cell proliferation in thymus21123.5×1e-04CDKN2A, ERBB2
regulation of DNA damage checkpoint2449.4×5e-04BRCA1, BRCA2
cellular response to ionizing radiation2164.4×0.003BRCA1, BRCA2
cellular senescence2118.3×0.004BRCA2, CDKN2A
epidermal growth factor receptor signaling pathway299.1×0.004BRAF, ERBB2
somatic stem cell population maintenance299.1×0.004BRAF, CDKN2A
double-strand break repair281.2×0.005BRCA1, BRCA2
double-strand break repair via homologous recombination262.4×0.008BRCA1, BRCA2
negative regulation of cell growth257.6×0.008BRCA1, CDKN2A
positive regulation of DNA-templated transcription316.8×0.008BRCA1, BRCA2, CDKN2A
nuclear body organization11685.2×0.008CDKN2A
mitotic recombination-dependent replication fork processing11685.2×0.008BRCA2
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment11123.5×0.010BRAF
apoptotic process involved in mammary gland involution11123.5×0.010CDKN2A
positive regulation of macrophage apoptotic process11123.5×0.010CDKN2A
positive regulation of apoptotic process involved in mammary gland involution1842.6×0.011CDKN2A
obsolete negative regulation of proteolysis involved in protein catabolic process1842.6×0.011CDKN2A
immature T cell proliferation in thymus1674.1×0.011ERBB2
positive regulation of axon regeneration1674.1×0.011BRAF
cellular response to indole-3-methanol1674.1×0.011BRCA1
negative regulation of synaptic vesicle exocytosis1674.1×0.011BRAF
ERBB2-ERBB4 signaling pathway1561.7×0.011ERBB2
chordate embryonic development1561.7×0.011BRCA1
CD4-positive, alpha-beta T cell differentiation1561.7×0.011BRAF
myeloid progenitor cell differentiation1481.5×0.011BRAF
positive regulation of smooth muscle cell apoptotic process1481.5×0.011CDKN2A
negative regulation of centriole replication1481.5×0.011BRCA1
mitochondrial depolarization1481.5×0.011CDKN2A
oncogene-induced cell senescence1481.5×0.011CDKN2A

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 2

Druggability breadth: 4 of 5 evidence-associated genes (80%) 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.

SymbolExample approved molecule
BRAFVEMURAFENIB
BRCA1RIBOFLAVIN
ERBB2CLOTRIMAZOLE

Top cohort targets by molecule count

SymbolMoleculesMax phase
ERBB2834
BRAF484
BRCA1124
BRCA200
CDKN2A00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
VEMURAFENIB4BRAF
PONATINIB4BRAF, ERBB2
FEDRATINIB4BRAF
SORAFENIB4BRAF, ERBB2
DASATINIB ANHYDROUS4BRAF
RUXOLITINIB4BRAF
INFIGRATINIB PHOSPHATE4BRAF
INFIGRATINIB4BRAF
REGORAFENIB4BRAF
DABRAFENIB4BRAF
COBIMETINIB4BRAF
NILOTINIB4BRAF
ABEMACICLIB4BRAF
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4BRAF
DASATINIB4BRAF, ERBB2
ERLOTINIB4BRAF, ERBB2
GEFITINIB4BRAF, ERBB2
IMATINIB4BRAF, ERBB2
RIBOFLAVIN4BRCA1
DAUNORUBICIN HYDROCHLORIDE4BRCA1
TOPOTECAN HYDROCHLORIDE4BRCA1
DAUNORUBICIN4BRCA1
DOXORUBICIN HYDROCHLORIDE4BRCA1
MESALAMINE4BRCA1
DIPYRIDAMOLE4BRCA1
CLOTRIMAZOLE4ERBB2
ERLOTINIB HYDROCHLORIDE4ERBB2
AFATINIB4ERBB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

SymbolAssaysType breakdown
BRAF1,442Binding:1400, Functional:37, ADMET:5
ERBB21,221Binding:1136, Functional:79, ADMET:6
BRCA113Binding:9, Functional:4
CDKN2A2Binding:2

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BRAF2.7.10.2, 2.7.11.1non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
BRCA12.3.2.27RING-type E3 ubiquitin transferase
ERBB22.7.10.1receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
BRAF1,442
ERBB21,221

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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.

CompoundMax phaseCohort target (bioactivity)
VEMURAFENIB4BRAF
PONATINIB4BRAF, ERBB2
FEDRATINIB4BRAF
SORAFENIB4BRAF, ERBB2
DASATINIB ANHYDROUS4BRAF
RUXOLITINIB4BRAF
INFIGRATINIB PHOSPHATE4BRAF
INFIGRATINIB4BRAF
REGORAFENIB4BRAF
DABRAFENIB4BRAF
COBIMETINIB4BRAF
NILOTINIB4BRAF
ABEMACICLIB4BRAF
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4BRAF
DASATINIB4BRAF, ERBB2
ERLOTINIB4BRAF, ERBB2
GEFITINIB4BRAF, ERBB2
IMATINIB4BRAF, ERBB2
RIBOFLAVIN4BRCA1
DAUNORUBICIN HYDROCHLORIDE4BRCA1
TOPOTECAN HYDROCHLORIDE4BRCA1
DAUNORUBICIN4BRCA1
DOXORUBICIN HYDROCHLORIDE4BRCA1
MESALAMINE4BRCA1
DIPYRIDAMOLE4BRCA1
CLOTRIMAZOLE4ERBB2
ERLOTINIB HYDROCHLORIDE4ERBB2
AFATINIB4ERBB2

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)3BRAF, BRCA1, ERBB2
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug2BRCA2, CDKN2A

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
BRCA20BRCA1
CDKN2A2—

Clinical trials & evidence

Clinical trials

Clinical trials: 294.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE2131
Not specified66
PHASE1/PHASE237
PHASE126
PHASE322
PHASE2/PHASE310
PHASE41
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06818773PHASE4NOT_YET_RECRUITINGInetetamab Plus Chemotherapy ± PD-1/PD-L1 in HER2+ Advanced Biliary Cancer
NCT05065957PHASE2/PHASE3RECRUITINGStudy of Combination Therapy of D07001-Softgel Capsules and Xeloda/TS-1 in Subjects With Advanced Biliary Tract Cancer
NCT05429697PHASE2/PHASE3RECRUITINGStudy of SMT-NK Inj. Plus Pembrolizumab vs Pembrolizumab Monotherapy in Patients With Advanced Biliary Tract Cancer
NCT05506943PHASE2/PHASE3ACTIVE_NOT_RECRUITINGA Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
NCT05771480PHASE3ACTIVE_NOT_RECRUITINGDurvalumab With Chemotherapy as First Line Treatment in Patients With Advanced Biliary Tract Cancers (aBTCs)
NCT06037980PHASE2/PHASE3RECRUITINGCisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative Chemotherapy Versus Immediate Resection in patIents With resecTable BiliarY Tract Cancers (BTC) at High Risk for Recurrence
NCT06109779PHASE3ACTIVE_NOT_RECRUITINGRilvegostomig + Chemotherapy as Adjuvant Therapy for Biliary Tract Cancer After Resection (ARTEMIDE-Biliary01)
NCT06282575PHASE3RECRUITINGEfficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer
NCT06467357PHASE3RECRUITINGPhase 3 Study of T-DXd and Rilvegostomig Versus SoC in Advanced HER2-expressing Biliary Tract Cancer
NCT06591520PHASE3ACTIVE_NOT_RECRUITINGAK112 Combined With Chemotherapy Versus Durvalumab Combined With Chemotherapy in Advanced Biliary Tract Cancer
NCT06622057PHASE3NOT_YET_RECRUITINGD07001 Softgel-Capsules and Capecitabine Combination Therapy in Patients With Advanced Biliary Tract Cancer
NCT06662877PHASE2/PHASE3NOT_YET_RECRUITINGAnlotinib Plus Nab-Paclitaxels and S-1 for Patients with Advanced Biliary Tract Cancer As Second-Line Treatment
NCT07062263PHASE3RECRUITINGTrastuzumab Plus Chemotherapy vs Chemotherapy Alone in First-line HER2 Positive Advanced Biliary Tract Cancer Patients
NCT07221253PHASE3RECRUITINGA Study of Rilvegostomig or Durvalumab Plus Chemotherapy for First-Line Treatment of Biliary Tract Cancer (ARTEMIDE-Biliary02)
NCT07229625PHASE3RECRUITINGA Phase III Study of SHR-8068 in Combination With Adebrelimab and Platinum-Containing Chemotherapy Versus Durvalumab in Combination With Platinum-Containing Chemotherapy as First-line Treatment for Advanced Biliary Tract Cancer (BTC)
NCT07265674PHASE3RECRUITINGA Study to Select a Dose Regimen (Part A) and to Investigate Overall Survival (Part B) With Nanvuranlat Compared With Physician’s Best Choice in Participants Aged 18 Years or Older With Biliary Tract Cancer
NCT07437287PHASE2/PHASE3NOT_YET_RECRUITINGTesting Mitazalimab in Combination With Standard Chemotherapy in Immunotherapy Resistant Advanced Biliary Tract Cancers
NCT07582315PHASE3NOT_YET_RECRUITINGA Study Comparing BL-B01D1 With Treatment of Physician’s Choice in Patients With Locally Advanced or Metastatic Biliary Tract Cancer After Failure of Platinum-based Chemotherapy and PD-1/PD-L1 Monoclonal Antibody Therapy(PANKU-BTC01)
NCT07606599PHASE3NOT_YET_RECRUITINGA Study of BL-M07D1 Versus Physician’s Choice of Chemotherapy in Patients With HER2-expressing Locally Advanced or Metastatic Biliary Tract Cancer After Platinum-containing Chemotherapy Failure
NCT00090025PHASE3TERMINATEDXL119 Versus 5-Fluorouracil (5-FU) Plus Leucovorin (LV) in Subjects With Advanced Biliary Tumors
NCT01470443PHASE3UNKNOWNStudy of GEMOX(Gemcitabine/Oxaliplatin) Versus XELOX(Xeloda/Oxaliplatin) in Advanced Biliary Tract Carcinoma
NCT01926236PHASE3COMPLETEDActive Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers
NCT02182778PHASE3COMPLETEDGEM/Cisplatin/S-1 vs GEM/Cisplatin for Biliary Tract Cancer
NCT02597465PHASE3WITHDRAWNA Randomized, Open-Label, Comparative, Parallel-Group, Multicenter Study of SPARC1507
NCT02988635PHASE3COMPLETEDEarly Palliative Care on Quality of Life of Advanced Cancer Patients
NCT03093870PHASE2/PHASE3COMPLETEDVarlitinib in Combination With Capecitabine for Advanced or Metastatic Biliary Tract Cancer
NCT03673072PHASE3COMPLETEDNeoadjuvant Chemotherapy With Gemcitabine Plus Cisplatin Followed by Radical Liver Resection Versus Immediate Radical Liver Resection Alone With or Without Adjuvant Chemotherapy in Incidentally Detected Gallbladder Carcinoma After Simple Cholecystectomy or in Front of Radical Resection of BTC
NCT03873532PHASE2/PHASE3UNKNOWNA Trial Evaluating Surufatinib Efficacy and Safety in Biliary Tract Carcinoma Patients
NCT04066491PHASE2/PHASE3TERMINATEDGemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC
NCT04163900PHASE3TERMINATEDComparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Advanced Biliary Tract Cancer
NCT04401709PHASE3UNKNOWNGemcitabine+ Capecitabine Vs Capecitabine in Curatively Resected Biliary Tract Cancer
NCT05487443PHASE2/PHASE3UNKNOWNThe Efficacy of Chemotherapy Combined With Immunocheckpoint Inhibitors in Advanced Biliary Malignancies
NCT05924880PHASE3COMPLETEDA Phase 3b, Open-label, Multi-center Study on Durvalumab in Combination With Gemcitabine-based Chemotherapy as 1L Treatment for the Chinese Patients With Unresectable Biliary Tract Cancers (BTC)
NCT02711553PHASE2ACTIVE_NOT_RECRUITINGA Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer
NCT03482102PHASE2ACTIVE_NOT_RECRUITINGDurvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer
NCT03801083PHASE2RECRUITINGAdoptive Transfer of Tumor Infiltrating Lymphocytes for Biliary Tract Cancers
NCT04005339PHASE2ACTIVE_NOT_RECRUITINGNAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer
NCT04781192PHASE1/PHASE2ACTIVE_NOT_RECRUITINGThe Purpose of This Trial is to Determine if Regorafenib Plus Durvalumab (MEDI4736) is Safe and Effective in Treatment of Chemo Refractory Advanced Biliary Tract Cancers
NCT04969887PHASE2ACTIVE_NOT_RECRUITINGCombination Immunotherapy in Rare Cancers Under InvesTigation
NCT05170438PHASE2ACTIVE_NOT_RECRUITINGLenvatinib Plus Paclitaxel for Patients With Advanced Biliary Tract Cancer Who Failed to Gemcitabine-based Treatment

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
OXALIPLATIN419
DURVALUMAB47
LEVOLEUCOVORIN43
TELOTRISTAT ETHYL42
BINIMETINIB41
DOSTARLIMAB41
FUTIBATINIB41
GEMCITABINE HYDROCHLORIDE41
IVOSIDENIB41
LENVATINIB41
MANGANESE CHLORIDE41
NIRAPARIB41
PEMETREXED DISODIUM41
RAMUCIRUMAB41
RUCAPARIB41
SIMVASTATIN41
TIPIRACIL41
TRASTUZUMAB DERUXTECAN41
TREMELIMUMAB41
TRIFLURIDINE41
VANDETANIB41
ZANIDATAMAB41
SURUFATINIB37
RILVEGOSTOMIG35
ADEBRELIMAB34
IVONESCIMAB34
BINTRAFUSP ALFA33
BRIGIMADLIN32
ENVAFOLIMAB32
FOSGEMCITABINE PALABENAMIDE32

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 5 predictive associations from 5 curated evidence items.

Molecular subtypeTherapyEffectLevelCIViC
BRAF V600EDabrafenib + TrametinibSensitivity/ResponseCIViC BEID7264
BRCA1 Mutation OR BRCA2 MutationOlaparibSensitivity/ResponseCIViC BEID12764
CDKN2A Loss OR CDKN2A MutationPalbociclibSensitivity/ResponseCIViC BEID11654
ERBB2 AmplificationPertuzumab + TrastuzumabSensitivity/ResponseCIViC BEID5983
PBRM1 Loss-of-functionNiraparibSensitivity/ResponseCIViC DEID12697

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 73

This page pulls from 73 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterprointogenmedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptuberonufeatureumlsuniprot