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Atlas / Disease / Ovarian serous adenocarcinoma

Ovarian serous adenocarcinoma

disease
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Also known as malignant ovarian serous tumourovarian serous carcinomaovary serous adenocarcinomaserous adenocarcinoma of ovaryserous adenocarcinoma of the ovaryserous carcinoma of ovaryserous carcinoma of the ovaryserous ovarian cancer

Summary

Ovarian serous adenocarcinoma (MONDO:0005211) is a disease with 9 cohort genes (11 GWAS associations across 1 studies) and 41 clinical trials. The dominant Reactome pathway is RAF activation (4 cohort genes). Molecularly, KRAS Mutation confers sensitivity to Avutometinib And Defactinib in Ovary Serous Adenocarcinoma (CIViC Level A); 11 further subtype–drug associations are mapped below. Top therapeutic interventions include paclitaxel, topotecan, and olaparib.

At a glance

  • Cohort genes: 9
  • GWAS associations: 11
  • Clinical trials: 41
  • Precision-medicine evidence (CIViC): 12 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameovarian serous adenocarcinoma
Mondo IDMONDO:0005211
EFOEFO:0002917
DOIDDOID:0050933, DOID:5744
NCITC7550
UMLSC1335177
MedGen233278
GARD0024164
Anatomy (UBERON)UBERON:0000992
Is cancer (heuristic)no

Also known as: malignant ovarian serous tumour · ovarian serous adenocarcinoma · ovarian serous carcinoma · ovary serous adenocarcinoma · serous adenocarcinoma of ovary · serous adenocarcinoma of the ovary · serous carcinoma of ovary · serous carcinoma of the ovary · serous ovarian cancer

Data availability: 11 GWAS associations (1 study) · 97 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (6): ovarian cystadenocarcinoma, rete ovarii adenocarcinoma, Krukenberg carcinoma, ovarian mucinous adenocarcinoma, ovarian clear cell adenocarcinoma, ovarian endometrioid adenocarcinoma

Subtypes (3): ovarian serous surface papillary adenocarcinoma, ovarian serous cystadenocarcinoma, primary peritoneal serous/papillary carcinoma

Genetics & variants

GWAS landscape

11 GWAS associations across 1 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
chr5:12859742e-21A1.32
chr8:1295419312e-15A0.7
chr5:12797902e-10T1.22
rs28536778e-10TERTA0.8
chr18:214258526e-09C0.84
chr10:1056943016e-08T0.24
chr17:360930221e-07G0.15
chr17:465006731e-07C0.16
chr2:1770426331e-07C0.15
chr3:1905255162e-07G0.16
rs14700533e-06BCL2L11, MIR4435-2HGT0.84

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90244169Dareng EO20242,749105,724Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic11

MAF distribution

BucketVariants
common (>=0.05)11
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
unknown9
intron_variant2

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
chr5:12859740.332e-21Tier 4: intronic/intergenic
chr8:1295419310.132e-15Tier 4: intronic/intergenic
chr5:12797900.2592e-10Tier 4: intronic/intergenic
rs285367751287079G>A,C,T0.49intron_variantTERT8e-10Tier 4: intronic/intergenic
chr18:214258520.386e-09Tier 4: intronic/intergenic
chr10:1056943010.16e-08Tier 4: intronic/intergenic
chr17:360930220.3771e-07Tier 4: intronic/intergenic
chr17:465006730.2681e-07Tier 4: intronic/intergenic
chr2:1770426330.321e-07Tier 4: intronic/intergenic
chr3:1905255160.3072e-07Tier 4: intronic/intergenic
rs14700532111158369G>C,T0.16intron_variantBCL2L11, MIR4435-2HG3e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 52 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
KRASOrphanet:1333Familial pancreatic carcinoma
KRASOrphanet:1340Cardiofaciocutaneous syndrome
KRASOrphanet:144Lynch syndrome
KRASOrphanet:146Differentiated thyroid carcinoma
KRASOrphanet:2396Encephalocraniocutaneous lipomatosis
KRASOrphanet:251615Pilomyxoid astrocytoma
KRASOrphanet:2612Linear nevus sebaceus syndrome
KRASOrphanet:268114RAS-associated autoimmune leukoproliferative disease
KRASOrphanet:3339Oculoectodermal syndrome
KRASOrphanet:648Noonan syndrome
KRASOrphanet:86834Juvenile myelomonocytic leukemia
MAP2K1Orphanet:1340Cardiofaciocutaneous syndrome
MAP2K1Orphanet:389Langerhans cell histiocytosis
NRASOrphanet:146Differentiated thyroid carcinoma
NRASOrphanet:2612Linear nevus sebaceus syndrome
NRASOrphanet:268114RAS-associated autoimmune leukoproliferative disease
NRASOrphanet:389Langerhans cell histiocytosis
NRASOrphanet:626Large/giant congenital melanocytic nevus

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only9

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
AURKAHGNC:11393ENSG00000087586O14965Aurora kinase Acivic_evidence
CD274HGNC:17635ENSG00000120217Q9NZQ7Programmed cell death 1 ligand 1civic_evidence
CDK12HGNC:24224ENSG00000167258Q9NYV4Cyclin-dependent kinase 12civic_evidence
KRASHGNC:6407ENSG00000133703P01116GTPase KRascivic_evidence
MAP2K1HGNC:6840ENSG00000169032Q02750Dual specificity mitogen-activated protein kinase kinase 1civic_evidence
NRASHGNC:7989ENSG00000213281P01111GTPase NRascivic_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.
AURKAAurora kinase AMitotic serine/threonine kinase that contributes to the regulation of cell cycle progression.
CD274Programmed cell death 1 ligand 1Plays a critical role in induction and maintenance of immune tolerance to self.
CDK12Cyclin-dependent kinase 12Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation.
KRASGTPase KRasRas proteins bind GDP/GTP and possess intrinsic GTPase activity.
MAP2K1Dual specificity mitogen-activated protein kinase kinase 1Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway.
NRASGTPase NRasRas proteins bind GDP/GTP and possess intrinsic GTPase activity.

Protein-family classification

Druggable: 6 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.67

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
Kinase412.3×9e-04
Antibody/Immunoglobulin13.2×0.673
Enzyme (other)11.3×0.859
Transcription factor10.9×0.859
Other/Unknown20.4×0.992

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
AURKAKinaseyes2.7.11.1Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CD274Antibody/ImmunoglobulinyesIg_sub, Ig-like_dom, Ig_V-set
CDK12Kinaseyes2.7.11.22Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
KRASEnzyme (other)yes3.6.5.2Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MAP2K1Kinaseyes2.7.12.2Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
NRASOther/UnknownnoSmall_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

Expression context

Cohort genes with no expression data: 0.

9 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)9
unknown0

Top tissues across cohort

TissueCohort genes
secondary oocyte5
ventricular zone3
buccal mucosa cell2
male germ line stem cell (sensu Vertebrata) in testis2
oocyte2
calcaneal tendon1
colonic epithelium1
primordial germ cell in gonad1
cartilage tissue1
lower lobe of lung1
placenta1
sural nerve1
nipple1
pylorus1
trigeminal ganglion1
orbitofrontal cortex1
epithelium of nasopharynx1
gingival epithelium1

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
AURKA236ubiquitousmarkeroocyte, secondary oocyte, ventricular zone
CD274208ubiquitousmarkercartilage tissue, placenta, lower lobe of lung
CDK12259ubiquitousmarkerbuccal mucosa cell, sural nerve, secondary oocyte
KRAS298ubiquitousmarkertrigeminal ganglion, pylorus, nipple
MAP2K1298ubiquitousmarkersecondary oocyte, oocyte, orbitofrontal cortex
NRAS278ubiquitousmarkergingival epithelium, epithelium of nasopharynx, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 11.

Hub genes (top 10 by interactor count)

SymbolInteractor count
KRAS14,509
BRCA19,064
NRAS7,598
BRAF7,394
AURKA6,376
MAP2K15,944
CD2745,012
BRCA24,839
CDK122,938

Intra-cohort edges

ABSources
AURKABRCA1string_interaction
BRAFBRCA2biogrid_interaction
BRAFKRASbiogrid_interaction, intact, string_interaction
BRAFMAP2K1biogrid_interaction, intact, string_interaction
BRAFNRASbiogrid_interaction, intact, string_interaction
BRCA1BRCA2string_interaction
BRCA1CDK12string_interaction
BRCA2CDK12string_interaction
KRASMAP2K1biogrid_interaction, string_interaction
KRASNRASintact
MAP2K1NRASstring_interaction

Structural data

PDB: 9 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
KRASP01116511
AURKAO14965193
BRAFP15056131
MAP2K1Q0275094
CD274Q9NZQ776
CDK12Q9NYV439
NRASP0111135
BRCA1P3839833
BRCA2P5158714

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 219. Enrichment computed across 9 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
RAF activation4149.3×7e-07BRAF, KRAS, MAP2K1, NRAS
Signaling by high-kinase activity BRAF mutants4141.0×7e-07BRAF, KRAS, MAP2K1, NRAS
MAP2K and MAPK activation4126.9×7e-07BRAF, KRAS, MAP2K1, NRAS
Signaling by RAF1 mutants4123.8×7e-07BRAF, KRAS, MAP2K1, NRAS
Negative regulation of MAPK pathway4118.0×7e-07BRAF, KRAS, MAP2K1, NRAS
Signaling by moderate kinase activity BRAF mutants4112.8×7e-07BRAF, KRAS, MAP2K1, NRAS
Paradoxical activation of RAF signaling by kinase inactive BRAF4112.8×7e-07BRAF, KRAS, MAP2K1, NRAS
Signaling downstream of RAS mutants4112.8×7e-07BRAF, KRAS, MAP2K1, NRAS
Signaling by BRAF and RAF1 fusions475.8×3e-06BRAF, KRAS, MAP2K1, NRAS
Signaling by RAS GAP mutants2845.9×3e-05KRAS, NRAS
Signaling by RAS GTPase mutants2845.9×3e-05KRAS, NRAS
Activation of RAS in B cells2507.6×1e-04KRAS, NRAS
Negative feedback regulation of MAPK pathway2423.0×1e-04BRAF, MAP2K1
RAF/MAP kinase cascade427.1×1e-04BRAF, KRAS, MAP2K1, NRAS
RAS signaling downstream of NF1 loss-of-function variants2362.5×2e-04KRAS, NRAS
Estrogen-stimulated signaling through PRKCZ2362.5×2e-04KRAS, NRAS
SOS-mediated signalling2317.2×2e-04KRAS, NRAS
Prolonged ERK activation events2317.2×2e-04BRAF, MAP2K1
Activated NTRK3 signals through RAS2282.0×2e-04KRAS, NRAS
EGFR Transactivation by Gastrin2253.8×2e-04KRAS, NRAS
SHC-related events triggered by IGF1R2253.8×2e-04KRAS, NRAS
Activated NTRK2 signals through RAS2253.8×2e-04KRAS, NRAS
MET activates RAS signaling2230.7×3e-04KRAS, NRAS
Frs2-mediated activation2211.5×3e-04BRAF, MAP2K1
Signaling by FGFR4 in disease2211.5×3e-04KRAS, NRAS
Activated NTRK2 signals through FRS2 and FRS32211.5×3e-04KRAS, NRAS
Constitutive Signaling by Overexpressed ERBB22211.5×3e-04KRAS, NRAS
Defective homologous recombination repair (HRR) due to PALB2 loss of function2211.5×3e-04BRCA1, BRCA2
p38MAPK events2195.2×3e-04KRAS, NRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants2195.2×3e-04KRAS, NRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
MAPK cascade468.1×5e-05BRAF, KRAS, MAP2K1, NRAS
negative regulation of intracellular estrogen receptor signaling pathway2249.7×0.002BRCA1, CDK12
regulation of DNA damage checkpoint2249.7×0.002BRCA1, BRCA2
face development2178.3×0.002BRAF, MAP2K1
positive regulation of gene expression417.2×0.002BRAF, BRCA1, KRAS, MAP2K1
positive regulation of axonogenesis2129.1×0.004BRAF, MAP2K1
thyroid gland development2120.8×0.004BRAF, MAP2K1
positive regulation of mitotic cell cycle2104.0×0.005BRCA2, AURKA
regulation of cytokinesis293.6×0.005BRCA2, AURKA
cellular response to ionizing radiation291.3×0.005BRCA1, BRCA2
thymus development274.9×0.006BRAF, MAP2K1
response to glucocorticoid272.0×0.006KRAS, MAP2K1
ERK1 and ERK2 cascade270.7×0.006BRAF, MAP2K1
visual learning268.1×0.006BRAF, KRAS
positive regulation of transcription elongation by RNA polymerase II266.9×0.006CDK12, MAP2K1
cellular senescence265.7×0.006BRCA2, MAP2K1
response to mineralocorticoid11872.4×0.006KRAS
negative regulation of tumor necrosis factor superfamily cytokine production11872.4×0.006CD274
positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process11872.4×0.006CD274
Ras protein signal transduction245.7×0.009KRAS, NRAS
double-strand break repair245.1×0.009BRCA1, BRCA2
negative regulation of homotypic cell-cell adhesion1936.2×0.010MAP2K1
Golgi inheritance1936.2×0.010MAP2K1
mitotic recombination-dependent replication fork processing1936.2×0.010BRCA2
cerebellar cortex formation1624.1×0.012MAP2K1
forebrain astrocyte development1624.1×0.012KRAS
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment1624.1×0.012BRAF
positive regulation of oocyte maturation1624.1×0.012AURKA
positive regulation of endodermal cell differentiation1624.1×0.012MAP2K1
double-strand break repair via homologous recombination234.7×0.012BRCA1, BRCA2

Therapeutics

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 7 · Phased (≥1): 8 · Undrugged: 1

Druggability breadth: 8 of 9 evidence-associated genes (89%) 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
AURKAINAMRINONE
CD274MOCLOBEMIDE
KRASVEMURAFENIB
MAP2K1VEMURAFENIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
AURKA654
MAP2K1544
BRAF484
CDK12173
BRCA1124
KRAS114
CD27444
NRAS11
BRCA200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
VEMURAFENIB4BRAF, KRAS, MAP2K1
PONATINIB4BRAF
FEDRATINIB4AURKA, BRAF, MAP2K1
SORAFENIB4AURKA, BRAF, MAP2K1
DASATINIB ANHYDROUS4BRAF
RUXOLITINIB4BRAF, MAP2K1
INFIGRATINIB PHOSPHATE4BRAF
INFIGRATINIB4BRAF
REGORAFENIB4BRAF
DABRAFENIB4BRAF, KRAS
COBIMETINIB4BRAF, MAP2K1
NILOTINIB4BRAF
ABEMACICLIB4BRAF
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4AURKA, BRAF
DASATINIB4AURKA, BRAF, MAP2K1
ERLOTINIB4AURKA, BRAF
GEFITINIB4BRAF
IMATINIB4BRAF
RIBOFLAVIN4BRCA1
DAUNORUBICIN HYDROCHLORIDE4BRCA1
TOPOTECAN HYDROCHLORIDE4BRCA1
DAUNORUBICIN4BRCA1
DOXORUBICIN HYDROCHLORIDE4BRCA1
MESALAMINE4BRCA1
DIPYRIDAMOLE4BRCA1
INAMRINONE4AURKA
AXITINIB4AURKA, MAP2K1
NICLOSAMIDE4AURKA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

SymbolAssaysType breakdown
AURKA1,500Binding:1483, Functional:10, ADMET:7
BRAF1,442Binding:1400, Functional:37, ADMET:5
MAP2K11,200Binding:1150, Functional:47, ADMET:3
KRAS861Binding:829, Functional:32
CD274525Binding:520, Functional:5
CDK12347Binding:341, Functional:6
NRAS18Binding:18
BRCA113Binding:9, Functional:4

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
AURKA2.7.11.1non-specific serine/threonine protein kinase
CDK122.7.11.22, 2.7.11.23cyclin-dependent kinase, [RNA-polymerase]-subunit kinase
KRAS3.6.5.2small monomeric GTPase
MAP2K12.7.12.2mitogen-activated protein kinase kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
BRAF1,442
AURKA1,500
CD274525
CDK12347
KRAS861
MAP2K11,200

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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.

CompoundMax phaseCohort target (bioactivity)
VEMURAFENIB4BRAF, KRAS, MAP2K1
PONATINIB4BRAF
FEDRATINIB4AURKA, BRAF, MAP2K1
SORAFENIB4AURKA, BRAF, MAP2K1
DASATINIB ANHYDROUS4BRAF
RUXOLITINIB4BRAF, MAP2K1
INFIGRATINIB PHOSPHATE4BRAF
INFIGRATINIB4BRAF
REGORAFENIB4BRAF
DABRAFENIB4BRAF, KRAS
COBIMETINIB4BRAF, MAP2K1
NILOTINIB4BRAF
ABEMACICLIB4BRAF
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4AURKA, BRAF
DASATINIB4AURKA, BRAF, MAP2K1
ERLOTINIB4AURKA, BRAF
GEFITINIB4BRAF
IMATINIB4BRAF
RIBOFLAVIN4BRCA1
DAUNORUBICIN HYDROCHLORIDE4BRCA1
TOPOTECAN HYDROCHLORIDE4BRCA1
DAUNORUBICIN4BRCA1
DOXORUBICIN HYDROCHLORIDE4BRCA1
MESALAMINE4BRCA1
DIPYRIDAMOLE4BRCA1
INAMRINONE4AURKA
AXITINIB4AURKA, MAP2K1
NICLOSAMIDE4AURKA

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)6BRAF, BRCA1, AURKA, CD274, KRAS, MAP2K1
BPhased (≥1) drug, not yet approved2CDK12, NRAS
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1BRCA2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
BRCA20BRCA1

Clinical trials & evidence

Clinical trials

Clinical trials: 41.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE213
PHASE38
PHASE1/PHASE27
PHASE17
PHASE2/PHASE32
EARLY_PHASE12
Not specified2

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00565851PHASE3ACTIVE_NOT_RECRUITINGCarboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
NCT01167712PHASE3ACTIVE_NOT_RECRUITINGPaclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
NCT02502266PHASE2/PHASE3ACTIVE_NOT_RECRUITINGTesting the Combination of Cediranib and Olaparib in Comparison to Each Drug Alone or Other Chemotherapy in Recurrent Platinum-Resistant Ovarian Cancer
NCT04498117PHASE3ACTIVE_NOT_RECRUITINGOregovomab Plus Chemo in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery
NCT04575935PHASE3RECRUITINGMinimally Invasive Surgery After Neoadjuvant Chemotherapy for the Treatment of Stage IIIC-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer, LANCE Trial
NCT00108745PHASE3UNKNOWNPaclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer
NCT00262847PHASE3COMPLETEDCarboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
NCT00719303PHASE3UNKNOWNDiet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT00951496PHASE3COMPLETEDBevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
NCT02101788PHASE2/PHASE3COMPLETEDTrametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer
NCT01116648PHASE1/PHASE2ACTIVE_NOT_RECRUITINGCediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer
NCT02068794PHASE1/PHASE2ACTIVE_NOT_RECRUITINGMV-NIS Infected Mesenchymal Stem Cells in Treating Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer
NCT04034927PHASE2ACTIVE_NOT_RECRUITINGTesting the Addition of an Immunotherapy Drug, Tremelimumab, to the PARP Inhibition Drug, Olaparib, for Recurrent Ovarian, Fallopian Tube or Peritoneal Cancer
NCT04919629PHASE2RECRUITINGAPL-2 and Pembrolizumab Versus APL-2, Pembrolizumab and Bevacizumab Versus Bevacizumab Alone for the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer and Malignant Effusion
NCT05113368PHASE2RECRUITINGRegorafenib Combined With Fulvestrant in Recurrent Low-Grade Serous Ovarian Cancer
NCT05231122PHASE2RECRUITINGPembrolizumab Combined With Bevacizumab With or Without Agonist Anti-CD40 CDX-1140 for the Treatment of Patients With Recurrent Ovarian Cancer
NCT05451849PHASE1/PHASE2ACTIVE_NOT_RECRUITINGA Phase 1/2 Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer
NCT05605535PHASE2ACTIVE_NOT_RECRUITINGOregovomab Plus Chemotherapy in Neo-adjuvant Setting in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer
NCT07068178PHASE2NOT_YET_RECRUITINGEvaluating the Efficacy of Hyperthermic Intraperitoneal Treatment to Enhance the Sensitivity of Immune Checkpoint Inhibitor in Patients With Advanced Ovarian Cancer： A Single-arm Study
NCT00888615PHASE2COMPLETEDElesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
NCT01097746PHASE2COMPLETEDFirst-Line Treatment of Bevacizumab, Carboplatin, and Paclitaxel in Treating Participants With Stage III-IV Ovarian, Primary Peritoneal, and Fallopian Tube Cancer
NCT02364713PHASE2TERMINATEDMV-NIS or Investigator’s Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer
NCT02853318PHASE2COMPLETEDPembrolizumab, Bevacizumab, and Cyclophosphamide in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT02923739PHASE2TERMINATEDPaclitaxel and Bevacizumab With or Without Emactuzumab in Treating Patients With Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT02953457PHASE2COMPLETEDOlaparib, Durvalumab, and Tremelimumab in Treating Patients With Recurrent or Refractory Ovarian, Fallopian Tube or Primary Peritoneal Cancer With BRCA1 or BRCA2 Mutation
NCT03648489PHASE2COMPLETEDDual mTorc Inhibition in advanCed/Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer (of Clear Cell, Endometrioid and High Grade Serous Type, and Carcinosarcoma)
NCT05001282PHASE1/PHASE2TERMINATEDA Study to Evaluate ELU001 in Patients With Solid Tumors That Overexpress Folate Receptor Alpha (FRα)
NCT05074472PHASE1/PHASE2COMPLETEDA Phase 1/2, First-in-Human, Open Label, Dose Escalation Study Of A CSP Targeting Functional Antibody in Solid Tumors
NCT05538624PHASE1/PHASE2TERMINATEDA Study of Intraperitoneally Administered AVB-001 in Patients With Serous Adenocarcinoma of the Ovary
NCT06055348PHASE1/PHASE2UNKNOWNSC0191 Plus Chemotherapy in Advanced Ovarian Canceradvanced Ovarian Cancer
NCT05057715PHASE1ACTIVE_NOT_RECRUITINGhuCART-meso + VCN-01 in Pancreatic and Ovarian Cancer
NCT00989651PHASE1COMPLETEDCarboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
NCT01074411PHASE1COMPLETEDIntraperitoneal Bortezomib and Carboplatin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
NCT02020707PHASE1COMPLETEDNab-Paclitaxel and Bevacizumab in Treating Patients With Unresectable Stage IV Melanoma or Gynecological Cancers
NCT02179970PHASE1COMPLETEDTo Assess the Safety of Continuous IV Administration of Plerixafor in Patients With Advanced Pancreatic, Ovarian and Colorectal Cancers
NCT02627430PHASE1WITHDRAWNTalazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer
NCT02898207PHASE1COMPLETEDOlaparib and Onalespib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer
NCT05415709EARLY_PHASE1RECRUITINGHyperthermic Intraperitoneal Chemotherapy With Cisplatin During Surgery or Cisplatin Before Surgery for the Treatment of Stage III or IV Ovarian, Fallopian Tube or Peritoneal Cancer
NCT01504126EARLY_PHASE1COMPLETEDPropranolol Hydrochloride and Chemotherapy in Treating Patients With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
NCT02016833Not specifiedCOMPLETEDDevelopment of Immunological Assays for the Evaluation of Tumor Antigen Specific Immunity

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
PACLITAXEL417
TOPOTECAN44
OLAPARIB43
TRAMETINIB42
BEVACIZUMAB41
GEMCITABINE41
LETROZOLE41
PEGCETACOPLAN41
PLERIXAFOR41
TREMELIMUMAB41
CEDIRANIB34
OREGOVOMAB32
VELIPARIB32
ELESCLOMOL31
EMACTUZUMAB31
PACLITAXEL POLIGLUMEX31
IBENTATUG21
ONALESPIB21
SC-019121
PASIFOLATE EXATECAN11
CHEMBL376481601
CHEMBL572479801
S-ROLIPRAM01

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 12 predictive associations from 12 curated evidence items; also 1 prognostic.

Molecular subtypeTherapyEffectLevelCIViC
KRAS MutationAvutometinib And DefactinibSensitivity/ResponseCIViC AEID12818
BRCA1 MutationOlaparibSensitivity/ResponseCIViC BEID6333
BRCA2 MutationOlaparibSensitivity/ResponseCIViC BEID6334
EMSY OverexpressionPaclitaxel + Bevacizumab + CarboplatinSensitivity/ResponseCIViC BEID12149
KRAS MutationBinimetinibSensitivity/ResponseCIViC BEID8773
AURKA OverexpressionPlatinum CompoundResistanceCIViC BEID1650
BRAF V600EVemurafenibSensitivity/ResponseCIViC CEID3787
BRAF::CUL1 FusionMitogen-Activated Protein Kinase Kinase InhibitorSensitivity/ResponseCIViC CEID1662
KRAS MutationTrametinibSensitivity/ResponseCIViC CEID8932
MAP2K1 Q56_V60delSelumetinibSensitivity/ResponseCIViC CEID1661
NRAS Q61KTrametinibSensitivity/ResponseCIViC CEID8933
CDK12 Loss-of-functionOlaparibSensitivity/ResponseCIViC DEID623

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 72

This page pulls from 72 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptuberonufeatureumlsuniprot