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Atlas / Disease / Castration-resistant prostate carcinoma

Castration-resistant prostate carcinoma

disease
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Summary

Castration-resistant prostate carcinoma (MONDO:0850353) is a cancer with 13 cohort genes (13 CIViC-evidence somatic drivers) and 74 clinical trials. The dominant Reactome pathway is Impaired BRCA2 binding to PALB2 (8 cohort genes). Molecularly, ATM Mutation confers sensitivity to Olaparib in Castration-resistant Prostate Carcinoma (CIViC Level A); 22 further subtype–drug associations are mapped below. Top therapeutic interventions include enzalutamide, cabozantinib, and cabazitaxel.

At a glance

  • Classification: Cancer
  • Cohort genes: 13
  • Clinical trials: 74
  • Precision-medicine evidence (CIViC): 23 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namecastration-resistant prostate carcinoma
Mondo IDMONDO:0850353
DOIDDOID:0080909
NCITC130234
UMLSC1328504
MedGen730224
Is cancer (heuristic)yes

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › prostate carcinoma › castration-resistant prostate carcinoma

Related subtypes (8): prostate squamous cell carcinoma, primary prostate urothelial carcinoma, metastatic prostate carcinoma, prostate adenocarcinoma, grade III prostatic intraepithelial neoplasia, prostate small cell carcinoma, familial prostate carcinoma, hormone-resistant prostate carcinoma

Genetics & variants

GWAS landscape

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

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 45 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
BRCA1LoFBLCA,BRCA,MEL,OVTCIViC #6
BRCA2LoFBLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVACIViC #7
CHEK2ActBRCACIViC #8950
CHEK1CIViC #981
BRIP1CIViC #15955
CDK12LoFBLCA,CCRCC,CESC,DLBCLNOS,MEL,OVT,PRAD,PROSTATE,STADCIViC #12112
PALB2LoFOVTCIViC #15013
ATMLoFBLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTCCIViC #69
PPP2R2ACIViC #4465
BARD1ActPRADCIViC #549
RAD51BCIViC #4763
RAD51DCIViC #4765
RAD54LCIViC #6676

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare 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
CHEK2Orphanet:1331Familial prostate cancer
CHEK2Orphanet:145Hereditary breast and/or ovarian cancer syndrome
CHEK2Orphanet:440437Familial colorectal cancer Type X
CHEK2Orphanet:524Li-Fraumeni syndrome
CHEK2Orphanet:668Osteosarcoma
BRIP1Orphanet:145Hereditary breast and/or ovarian cancer syndrome
BRIP1Orphanet:84Fanconi anemia
PALB2Orphanet:1333Familial pancreatic carcinoma
PALB2Orphanet:145Hereditary breast and/or ovarian cancer syndrome
PALB2Orphanet:178Chordoma
PALB2Orphanet:227535Hereditary breast cancer
PALB2Orphanet:84Fanconi anemia
ATMOrphanet:100Ataxia-telangiectasia
ATMOrphanet:1331Familial prostate cancer
ATMOrphanet:145Hereditary breast and/or ovarian cancer syndrome
ATMOrphanet:227535Hereditary breast cancer
ATMOrphanet:370109Ataxia-telangiectasia variant
ATMOrphanet:440437Familial colorectal cancer Type X
ATMOrphanet:52416Mantle cell lymphoma
ATMOrphanet:67038B-cell chronic lymphocytic leukemia
BARD1Orphanet:145Hereditary breast and/or ovarian cancer syndrome
RAD51DOrphanet:1331Familial prostate cancer
RAD51DOrphanet:145Hereditary breast and/or ovarian cancer syndrome
RAD54LOrphanet:227535Hereditary breast cancer

Cohort genes → proteins

13 cohort genes, 13 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only13

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
BRCA1HGNC:1100ENSG00000012048P38398Breast cancer type 1 susceptibility proteincivic_evidence
BRCA2HGNC:1101ENSG00000139618P51587Breast cancer type 2 susceptibility proteincivic_evidence
CHEK2HGNC:16627ENSG00000183765O96017Serine/threonine-protein kinase Chk2civic_evidence
CHEK1HGNC:1925ENSG00000149554O14757Serine/threonine-protein kinase Chk1civic_evidence
BRIP1HGNC:20473ENSG00000136492Q9BX63Fanconi anemia group J proteincivic_evidence
CDK12HGNC:24224ENSG00000167258Q9NYV4Cyclin-dependent kinase 12civic_evidence
PALB2HGNC:26144ENSG00000083093Q86YC2Partner and localizer of BRCA2civic_evidence
ATMHGNC:795ENSG00000149311Q13315Serine-protein kinase ATMcivic_evidence
PPP2R2AHGNC:9304ENSG00000221914P63151Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoformcivic_evidence
BARD1HGNC:952ENSG00000138376Q99728BRCA1-associated RING domain protein 1civic_evidence
RAD51BHGNC:9822ENSG00000182185O15315DNA repair protein RAD51 homolog 2civic_evidence
RAD51DHGNC:9823ENSG00000185379O75771DNA repair protein RAD51 homolog 4civic_evidence
RAD54LHGNC:9826ENSG00000085999Q92698DNA repair and recombination protein RAD54-likecivic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
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.
CHEK2Serine/threonine-protein kinase Chk2Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
CHEK1Serine/threonine-protein kinase Chk1Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA.
BRIP1Fanconi anemia group J proteinDNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of chromosomal stability.
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.
PALB2Partner and localizer of BRCA2Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
ATMSerine-protein kinase ATMSerine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.
PPP2R2ASerine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoformSubstrate-recognition subunit of protein phosphatase 2A (PP2A) that plays a key role in cell cycle by controlling mitosis entry and exit.
BARD1BRCA1-associated RING domain protein 1E3 ubiquitin-protein ligase.
RAD51BDNA repair protein RAD51 homolog 2Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.
RAD51DDNA repair protein RAD51 homolog 4Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.
RAD54LDNA repair and recombination protein RAD54-likeMultifunctional ATPase that plays a role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks.

Protein-family classification

Druggable: 6 · Difficult: 4 · Unknown: 3 · 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.

FamilyGenesFoldFDR
Kinase48.5×0.005
Scaffold/PPI22.7×0.428
Enzyme (other)21.8×0.494
Transcription factor21.3×0.599
Other/Unknown30.4×0.997

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
BRCA1Transcription factorno2.3.2.27BRCT_dom, Znf_RING, BRCA1
BRCA2Other/UnknownnoBRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
CHEK2Kinaseyes2.7.11.1FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
CHEK1Kinaseyes2.7.11.1Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BRIP1Enzyme (other)yes3.6.4.12Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
CDK12Kinaseyes2.7.11.22Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
PALB2Scaffold/PPInoWD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
ATMKinaseyes2.7.11.1PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
PPP2R2AScaffold/PPInoPP2A_PR55, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
BARD1Transcription factorno2.3.2.27BRCT_dom, Znf_RING, Ankyrin_rpt
RAD51BOther/UnknownnoAAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like
RAD51DOther/UnknownnoAAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like
RAD54LEnzyme (other)yes3.6.4.B9SNF2_N, Helicase_C-like, Helicase_ATP-bd

Expression context

Cohort genes with no expression data: 0.

10 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)13
unknown0

Top tissues across cohort

TissueCohort genes
male germ line stem cell (sensu Vertebrata) in testis5
secondary oocyte5
primordial germ cell in gonad4
ventricular zone4
oocyte4
buccal mucosa cell3
sural nerve2
calcaneal tendon2
tongue squamous epithelium2
lower esophagus mucosa1
colonic epithelium1
corpus callosum1
esophagus mucosa1
male germ cell1
sperm1
left testis1
right testis1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
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
CHEK2183ubiquitousmarkerprimordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
CHEK1210ubiquitousmarkersecondary oocyte, oocyte, primordial germ cell in gonad
BRIP1181ubiquitousmarkerventricular zone, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
CDK12259ubiquitousmarkerbuccal mucosa cell, sural nerve, secondary oocyte
PALB2232ubiquitousyessecondary oocyte, buccal mucosa cell, oocyte
ATM286ubiquitousmarkercalcaneal tendon, colonic epithelium, corpus callosum
PPP2R2A297ubiquitousmarkercalcaneal tendon, esophagus mucosa, tongue squamous epithelium
BARD1271ubiquitousmarkersecondary oocyte, oocyte, tongue squamous epithelium
RAD51B193ubiquitousmarkersural nerve, buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis
RAD51D187ubiquitousyessperm, male germ cell, oocyte
RAD54L173ubiquitousyesleft testis, right testis, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 43.

Hub genes (top 10 by interactor count)

SymbolInteractor count
BRCA19,064
ATM7,383
PALB25,641
CHEK14,939
BRCA24,839
CHEK24,795
BARD14,230
RAD51D3,089
RAD51B2,993
CDK122,938

Intra-cohort edges

ABSources
ATMBARD1string_interaction
ATMBRCA1string_interaction
ATMBRCA2string_interaction
ATMCDK12string_interaction
ATMCHEK1string_interaction
ATMCHEK2string_interaction
ATMRAD51Dstring_interaction
ATMRAD54Lstring_interaction
BARD1BRCA1biogrid_interaction, intact, string_interaction
BARD1BRCA2string_interaction
BARD1BRIP1biogrid_interaction
BARD1CHEK2string_interaction
BARD1PALB2string_interaction
BARD1RAD51Bstring_interaction
BARD1RAD51Dstring_interaction
BRCA1BRCA2string_interaction
BRCA1BRIP1biogrid_interaction, intact, string_interaction
BRCA1CDK12string_interaction
BRCA1CHEK1string_interaction
BRCA1CHEK2string_interaction
BRCA1PALB2biogrid_interaction, intact, string_interaction
BRCA1RAD51Bstring_interaction
BRCA1RAD51Dstring_interaction
BRCA1RAD54Lstring_interaction
BRCA2BRIP1string_interaction
BRCA2CDK12string_interaction
BRCA2CHEK2string_interaction
BRCA2PALB2biogrid_interaction, intact, string_interaction
BRCA2RAD51Bstring_interaction
BRCA2RAD51Dstring_interaction
BRCA2RAD54Lstring_interaction
BRIP1PALB2string_interaction
CDK12PALB2string_interaction
CDK12RAD51Dstring_interaction
CHEK2PALB2string_interaction
CHEK2RAD51Dstring_interaction
CHEK2RAD54Lstring_interaction
PALB2RAD51Bstring_interaction
PALB2RAD51Dstring_interaction
PALB2RAD54Lstring_interaction
RAD51BRAD51Dbiogrid_interaction, intact, string_interaction
RAD51BRAD54Lstring_interaction
RAD51DRAD54Lstring_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CHEK1O14757164
CDK12Q9NYV439
CHEK2O9601738
BRCA1P3839833
RAD51DO7577117
BRCA2P5158714
ATMQ1331514
BARD1Q9972811
PPP2R2AP6315110
RAD51BO153155
PALB2Q86YC24
BRIP1Q9BX633
RAD54LQ926981

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 107. 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.

PathwayCohort genesFoldFDRSample cohort genes
Impaired BRCA2 binding to PALB28304.5×4e-18BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1, RAD51B, RAD51D
Defective homologous recombination repair (HRR) due to BRCA1 loss of function8282.0×4e-18BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1, RAD51B, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function8282.0×4e-18BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1, RAD51B, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function8282.0×4e-18BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1, RAD51B, RAD51D
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)8262.5×6e-18BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1, RAD51B, RAD51D
Homologous DNA Pairing and Strand Exchange8253.8×7e-18BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1, RAD51B, RAD51D
Resolution of D-loop Structures through Holliday Junction Intermediates8200.3×5e-17BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1, RAD51B, RAD51D
Presynaptic phase of homologous DNA pairing and strand exchange8181.3×1e-16BRCA1, BRCA2, CHEK1, BRIP1, ATM, BARD1, RAD51B, RAD51D
HDR through Homologous Recombination (HRR)8126.9×2e-15BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1, RAD51B, RAD51D
Impaired BRCA2 binding to RAD515128.6×2e-09BRCA1, BRCA2, BRIP1, ATM, BARD1
G2/M DNA damage checkpoint660.1×2e-09BRCA1, CHEK2, CHEK1, BRIP1, ATM, BARD1
Regulation of TP53 Activity through Phosphorylation658.9×3e-09BRCA1, CHEK2, CHEK1, BRIP1, ATM, BARD1
Defective homologous recombination repair (HRR) due to PALB2 loss of function4317.2×3e-09BRCA1, BRCA2, ATM, BARD1
Diseases of DNA Double-Strand Break Repair4271.9×5e-09BRCA1, BRCA2, ATM, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function4271.9×5e-09BRCA1, BRCA2, ATM, BARD1
Resolution of D-Loop Structures4211.5×1e-08BRCA1, BRCA2, ATM, BARD1
Diseases of DNA repair4190.3×2e-08BRCA1, BRCA2, ATM, BARD1
TP53 Regulates Transcription of DNA Repair Genes575.5×2e-08BRCA1, CHEK1, CDK12, ATM, RAD51D
Processing of DNA double-strand break ends547.6×2e-07BRCA1, CHEK1, BRIP1, ATM, BARD1
Homology Directed Repair4102.9×2e-07BRCA1, BRCA2, ATM, BARD1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)4102.9×2e-07BRCA1, BRCA2, ATM, BARD1
HDR through Single Strand Annealing (SSA)497.6×3e-07BRCA1, BRIP1, ATM, BARD1
DNA Double-Strand Break Repair482.8×5e-07BRCA1, BRCA2, ATM, BARD1
Defective DNA double strand break response due to BRCA1 loss of function2951.7×4e-06BRCA1, BARD1
Defective DNA double strand break response due to BARD1 loss of function2951.7×4e-06BRCA1, BARD1
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks448.8×4e-06BRCA1, CHEK2, ATM, BARD1
DNA Double Strand Break Response3119.0×7e-06BRCA1, ATM, BARD1
DNA Repair432.8×2e-05BRCA1, BRCA2, ATM, BARD1
Meiosis371.4×3e-05BRCA1, BRCA2, ATM
Cell Cycle515.0×4e-05BRCA1, BRCA2, ATM, PPP2R2A, BARD1

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 termCohort genesFoldFDRSample cohort genes
double-strand break repair via homologous recombination784.0×1e-10BRCA1, BRCA2, PALB2, ATM, RAD51B, RAD51D, RAD54L
DNA repair734.4×3e-08BRCA1, CHEK1, BRIP1, BARD1, RAD51B, RAD51D, RAD54L
double-strand break repair578.1×2e-07BRCA1, BRCA2, CHEK2, BRIP1, ATM
reciprocal meiotic recombination4172.8×3e-07ATM, RAD51B, RAD51D, RAD54L
DNA damage checkpoint signaling4120.6×1e-06CHEK2, CHEK1, BRIP1, ATM
homologous recombination3324.1×2e-06BRCA1, BRIP1, BARD1
regulation of DNA damage checkpoint3259.3×4e-06BRCA1, BRCA2, BARD1
inner cell mass cell proliferation3228.8×5e-06BRCA2, CHEK1, PALB2
replicative senescence3228.8×5e-06CHEK2, CHEK1, ATM
signal transduction in response to DNA damage3185.2×8e-06CHEK2, CHEK1, ATM
mitotic G2/M transition checkpoint3185.2×8e-06BRCA1, CHEK1, BARD1
DNA damage response520.6×4e-05BRCA1, CHEK2, CHEK1, ATM, BARD1
mitotic G2 DNA damage checkpoint signaling3102.3×4e-05BRCA1, CHEK1, ATM
response to ionizing radiation394.8×5e-05BRCA1, ATM, RAD54L
cellular response to ionizing radiation394.8×5e-05BRCA1, BRCA2, BARD1
regulation of signal transduction by p53 class mediator388.4×5e-05CHEK2, CHEK1, ATM
DNA damage response, signal transduction by p53 class mediator382.7×6e-05BRCA2, CHEK2, ATM
intrinsic apoptotic signaling pathway in response to DNA damage374.8×8e-05BRCA1, CHEK2, ATM
DNA strand resection involved in replication fork processing2324.1×1e-04BRCA1, BARD1
regulation of cell cycle422.9×2e-04BRCA1, ATM, BARD1, RAD51D
telomere maintenance via recombination2235.7×3e-04BRCA2, RAD51D
negative regulation of intracellular estrogen receptor signaling pathway2172.8×5e-04BRCA1, CDK12
regulation of autophagosome assembly2172.8×5e-04CHEK2, ATM
protein K6-linked ubiquitination2152.5×6e-04BRCA1, BARD1
cellular response to stress2129.6×8e-04CHEK2, ATM
cellular response to gamma radiation292.6×0.001CHEK2, ATM
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator276.2×0.002BRCA2, CHEK2
determination of adult lifespan266.5×0.003ATM, RAD54L
nucleotide-excision repair258.9×0.003BRCA2, BRIP1
somitogenesis257.6×0.003PALB2, ATM

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 5 · Phased (≥1): 6 · Undrugged: 7

Druggability breadth: 7 of 13 evidence-associated genes (54%) 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
BRCA1RIBOFLAVIN
CHEK2NERATINIB
CHEK1FEDRATINIB
ATMAMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

SymbolMoleculesMax phase
CHEK1364
ATM354
CHEK2304
CDK12173
BRCA1124
RAD54L12
BRCA200
BRIP100
PALB200
PPP2R2A00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
RIBOFLAVIN4BRCA1
DAUNORUBICIN HYDROCHLORIDE4BRCA1
TOPOTECAN HYDROCHLORIDE4BRCA1
DAUNORUBICIN4BRCA1
DOXORUBICIN HYDROCHLORIDE4BRCA1
MESALAMINE4BRCA1
DIPYRIDAMOLE4ATM, BRCA1
NERATINIB4CHEK1, CHEK2
BOSUTINIB4CHEK1, CHEK2
BRIGATINIB4CHEK1, CHEK2
SUNITINIB4CHEK1, CHEK2
GEFITINIB4CHEK2
FEDRATINIB4CHEK1
PALBOCICLIB4CHEK1
NINTEDANIB4CHEK1
MIDOSTAURIN4CHEK1
AMIODARONE HYDROCHLORIDE4ATM
FURAZOLIDONE4ATM
ESTRADIOL ACETATE4ATM
NAFTIFINE HYDROCHLORIDE4ATM
METHYSERGIDE MALEATE4ATM
AMITRIPTYLINE HYDROCHLORIDE4ATM
XYLOMETAZOLINE HYDROCHLORIDE4ATM
FLUVOXAMINE MALEATE4ATM
ESTRADIOL VALERATE4ATM
PERMETHRIN4ATM
MITOTANE4ATM
TICLOPIDINE HYDROCHLORIDE4ATM
ENOXIMONE4ATM
METHYLENE BLUE ANHYDROUS4ATM

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

SymbolAssaysType breakdown
CHEK11,086Binding:1039, Functional:44, ADMET:3
CHEK2690Binding:687, Functional:2, ADMET:1
CDK12347Binding:341, Functional:6
ATM240Binding:233, Functional:5, ADMET:2
BRCA113Binding:9, Functional:4
PPP2R2A5Binding:5
RAD54L3Functional:2, Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BRCA12.3.2.27RING-type E3 ubiquitin transferase
CHEK22.7.11.1non-specific serine/threonine protein kinase
CHEK12.7.11.1non-specific serine/threonine protein kinase
BRIP13.6.4.12DNA helicase
CDK122.7.11.22, 2.7.11.23cyclin-dependent kinase, [RNA-polymerase]-subunit kinase
ATM2.7.11.1non-specific serine/threonine protein kinase
BARD12.3.2.27RING-type E3 ubiquitin transferase
RAD54L3.6.4.B9

Cohort genes with high screening signal

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

SymbolChEMBL assays
CHEK2690
CHEK11,086
CDK12347
ATM240

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).

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.

CompoundMax phaseCohort target (bioactivity)
RIBOFLAVIN4BRCA1
DAUNORUBICIN HYDROCHLORIDE4BRCA1
TOPOTECAN HYDROCHLORIDE4BRCA1
DAUNORUBICIN4BRCA1
DOXORUBICIN HYDROCHLORIDE4BRCA1
MESALAMINE4BRCA1
DIPYRIDAMOLE4ATM, BRCA1
BOSUTINIB4CHEK1, CHEK2
BRIGATINIB4CHEK1, CHEK2
SUNITINIB4CHEK1, CHEK2
GEFITINIB4CHEK2
FEDRATINIB4CHEK1
PALBOCICLIB4CHEK1
NINTEDANIB4CHEK1
MIDOSTAURIN4CHEK1
AMIODARONE HYDROCHLORIDE4ATM
FURAZOLIDONE4ATM
ESTRADIOL ACETATE4ATM
NAFTIFINE HYDROCHLORIDE4ATM
METHYSERGIDE MALEATE4ATM
AMITRIPTYLINE HYDROCHLORIDE4ATM
XYLOMETAZOLINE HYDROCHLORIDE4ATM
FLUVOXAMINE MALEATE4ATM
ESTRADIOL VALERATE4ATM
PERMETHRIN4ATM
MITOTANE4ATM
TICLOPIDINE HYDROCHLORIDE4ATM
ENOXIMONE4ATM
METHYLENE BLUE ANHYDROUS4ATM

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4BRCA1, CHEK2, CHEK1, ATM
BPhased (≥1) drug, not yet approved2CDK12, RAD54L
CDruggable family + PDB, no drug1BRIP1
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug6BRCA2, PALB2, PPP2R2A, BARD1, RAD51B, RAD51D

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
BRCA20BRCA1
BRIP10BRCA1
PALB20BRCA1
RAD51D0BRCA1
PPP2R2A5—
BARD10—
RAD51B0—

Clinical trials & evidence

Clinical trials

Clinical trials: 74.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE238
PHASE119
PHASE1/PHASE210
Not specified4
PHASE33

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04455750PHASE3ACTIVE_NOT_RECRUITINGA Clinical Study Evaluating The Benefit of Adding Rucaparib to Enzalutamide for Men With Metastatic Prostate Cancer That Has Become Resistant To Testosterone-Deprivation Therapy
NCT06470243PHASE3RECRUITINGTesting Whether the Addition of Carboplatin Chemotherapy to Cabazitaxel Chemotherapy Will Improve Outcomes Compared to Cabazitaxel Alone in People With Castrate-Resistant Prostate Cancer That Has Spread Beyond the Prostate to Other Parts of the Body
NCT05547386PHASE3COMPLETED68Ga-PSMA-11 PET/CT Screening Prior to 177Lu-PSMA-617 Therapy for Patients With Metastatic Castrate Resistant Prostate Cancer
NCT02312557PHASE2ACTIVE_NOT_RECRUITINGPembrolizumab in Treating Patients With Metastatic Castration Resistant Prostate Cancer Previously Treated With Enzalutamide
NCT02522715PHASE1/PHASE2ACTIVE_NOT_RECRUITINGEnzalutamide and Cabazitaxel in Treating Patients With Metastatic, Castration-Resistant Prostate Cancer
NCT02703623PHASE2ACTIVE_NOT_RECRUITINGAbiraterone Acetate, Prednisone, and Apalutamide With or Without Ipilimumab or Cabazitaxel and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
NCT02893917PHASE2ACTIVE_NOT_RECRUITINGTesting Two Oral Drugs Combination (Cediranib and Olaparib) Compared to a Single Drug (Olaparib) for Men With Advanced Prostate Cancer
NCT03217747PHASE1/PHASE2ACTIVE_NOT_RECRUITINGAvelumab, Utomilumab, Anti-OX40 Antibody PF-04518600, and Radiation Therapy in Treating Patients With Advanced Malignancies
NCT03317392PHASE1/PHASE2ACTIVE_NOT_RECRUITINGTesting the Safety of Different Doses of Olaparib Given Radium-223 for Men With Advanced Prostate Cancer With Bone Metastasis
NCT03344211PHASE2ACTIVE_NOT_RECRUITINGEnzalutamide With or Without Radium Ra 223 Dichloride in Patients With Metastatic, Castration-Resistant Prostate Cancer
NCT03419234PHASE2ACTIVE_NOT_RECRUITINGAbiraterone Acetate and Antiandrogen Therapy With or Without Cabazitaxel and Prednisone in Treating Patients With Metastatic, Castration-Resistant Prostate Cancer Previously Treated With Docetaxel
NCT03517969PHASE2ACTIVE_NOT_RECRUITINGM6620 and Carboplatin With or Without Docetaxel in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
NCT04471974PHASE2ACTIVE_NOT_RECRUITINGZEN-3694, Enzalutamide, and Pembrolizumab for the Treatment of Metastatic Castration-Resistant Prostate Cancer
NCT04550494PHASE2RECRUITINGMeasuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
NCT04592237PHASE2ACTIVE_NOT_RECRUITINGCabazitaxel, Carboplatin, and Cetrelimab Followed by Niraparib With or Without Cetrelimab for the Treatment of Aggressive Variant Metastatic Prostate Cancer
NCT05113537PHASE1/PHASE2RECRUITINGAbemaciclib Before 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer
NCT05168618PHASE2RECRUITINGCabozantinib and Atezolizumab for the Treatment of Metastatic Castration-Resistant Prostate Cancer
NCT05689021PHASE2ACTIVE_NOT_RECRUITINGCJNJ-67652000 and Prednisone for Treatment of Metastatic Castration-Resistant Prostate Cancer and SPOP Gene Mutations
NCT05828082PHASE2ACTIVE_NOT_RECRUITINGTesting the Effect of M1774 on Hard-to-Treat Refractory SPOP-mutant Prostate Cancer
NCT05924672PHASE2ACTIVE_NOT_RECRUITINGEfficacy of Ra-223 in PSMA PET Optimally Selected Patients
NCT06039371PHASE2RECRUITINGSupraphysiological Androgen to Enhance Treatment Activity in Metastatic Castration-Resistant Prostate Cancer, SPECTRA Study
NCT06145633PHASE2RECRUITINGVorinostat and 177Lu-PSMA-617 for the Treatment of PSMA-Low Metastatic Castration-Resistant Prostate Cancer
NCT06200103PHASE2RECRUITINGSchedule De-Escalation of 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer
NCT06236139PHASE1/PHASE2RECRUITINGCell Therapy (STEAP1 CART) With Enzalutamide for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer
NCT06288113PHASE2RECRUITINGRe-treatment With 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer, RE-LuPSMA Trial
NCT06616155PHASE1/PHASE2RECRUITINGRuxolitinib and Enzalutamide for the Treatment of Metastatic Castration-Resistant Prostate Cancer
NCT06632977PHASE2RECRUITINGTargeted Treatment for Metastatic Prostate Cancer, The PREDICT Trial
NCT01505868PHASE1/PHASE2COMPLETEDCabazitaxel With or Without Carboplatin in Treating Patients With Previously Treated Metastatic Castration-Resistant Prostate Cancer
NCT01576172PHASE2COMPLETEDAbiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
NCT01881867PHASE2COMPLETEDCYT107 After Vaccine Treatment (Provenge®) in Patients With Metastatic Castration-Resistant Prostate Cancer
NCT02099864PHASE2COMPLETEDGenetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy
NCT02555189PHASE1/PHASE2TERMINATEDEnzalutamide With Ribociclib in Treating Patients With Metastatic Castrate-Resistant, Chemotherapy Naive Prostate Cancer That Retains Retinoblastoma Expression
NCT02565901PHASE1/PHASE2TERMINATEDSirolimus, Docetaxel, and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
NCT02598895PHASE2COMPLETEDDocetaxel and Carboplatin in Treating Patients With Metastatic, Castration Resistant Prostate Cancer Containing Inactivated Genes in the BRCA 1/2 Pathway
NCT03204812PHASE2COMPLETEDDurvalumab and Tremelimumab in Treating Chemotherapy Naive Patients With Metastatic Castration-Resistant Prostate Cancer
NCT03360721PHASE2TERMINATEDApalutamide, Abiraterone Acetate, and Prednisone in Treating Participants With Metastatic Castration Resistant Prostate Cancer
NCT03406858PHASE2COMPLETEDPembro and HER2Bi-Armed Activated T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer
NCT03442556PHASE2TERMINATEDDocetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency
NCT03448458PHASE2COMPLETEDGallium Ga 68-DOTATATE PET/CT in Diagnosing Patients With Metastatic Castration Resistant Prostate Cancer
NCT03456804PHASE2COMPLETEDESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
ENZALUTAMIDE418
CABOZANTINIB48
CABAZITAXEL47
GALLIUM GA 68 GOZETOTIDE46
LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN44
RUCAPARIB44
APALUTAMIDE43
DACOMITINIB ANHYDROUS43
GOSERELIN43
LEUPROLIDE43
RADIUM RA 223 DICHLORIDE43
TESTOSTERONE CYPIONATE43
ERDAFITINIB42
ABIRATERONE ACETATE41
AVELUMAB41
CEDAZURIDINE41
COBIMETINIB41
COPANLISIB41
DAROLUTAMIDE41
DEGARELIX41
ENASIDENIB41
ENTRECTINIB41
FLUDEOXYGLUCOSE F 1841
HYALURONIDASE (HUMAN RECOMBINANT)41
IDELALISIB41
LORLATINIB41
LOSARTAN POTASSIUM41
NERATINIB41
NICLOSAMIDE41
NIRAPARIB41

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 23 predictive associations from 23 curated evidence items.

Molecular subtypeTherapyEffectLevelCIViC
ATM MutationOlaparibSensitivity/ResponseCIViC AEID8505
ATR Loss-of-functionTalazoparib + EnzalutamideSensitivity/ResponseCIViC AEID12217
BARD1 MutationOlaparibSensitivity/ResponseCIViC AEID11209
BRCA1 MutationOlaparibSensitivity/ResponseCIViC AEID11203
BRCA1 MutationTalazoparib + EnzalutamideSensitivity/ResponseCIViC AEID11734
BRCA1 Mutation OR BRCA2 MutationAbiraterone + NiraparibSensitivity/ResponseCIViC AEID11738
BRCA1 Mutation OR BRCA2 MutationRucaparibSensitivity/ResponseCIViC AEID12944
BRCA2 MutationTalazoparib + EnzalutamideSensitivity/ResponseCIViC AEID11733
BRCA2 MutationOlaparibSensitivity/ResponseCIViC AEID8842
BRIP1 MutationOlaparibSensitivity/ResponseCIViC AEID11208
CDK12 MutationOlaparibSensitivity/ResponseCIViC AEID11204
CDK12 MutationTalazoparib + EnzalutamideSensitivity/ResponseCIViC AEID11735
CHEK1 MutationOlaparibSensitivity/ResponseCIViC AEID11210
CHEK2 mutationOlaparibSensitivity/ResponseCIViC AEID11205
FANCL MutationOlaparibSensitivity/ResponseCIViC AEID11211
PALB2 MutationOlaparibSensitivity/ResponseCIViC AEID8504
RAD51B MutationOlaparibSensitivity/ResponseCIViC AEID11212
RAD51C MutationOlaparibSensitivity/ResponseCIViC AEID11213
RAD51D MutationOlaparibSensitivity/ResponseCIViC AEID11214
RAD54L MutationOlaparibSensitivity/ResponseCIViC AEID11207
ATM MutationEnzalutamide + TalazoparibSensitivity/ResponseCIViC BEID11736
CHEK2 mutationEnzalutamide + TalazoparibSensitivity/ResponseCIViC BEID11737
PPP2R2A MutationOlaparibSensitivity/ResponseCIViC BEID11206

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 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterprointogenmedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot