{"entity":{"id":"atr","kind":"target","name":"ATR","aka":[],"tldr":"ATR is a DNA-damage alarm kinase. Blocking it makes tumours with broken repair systems collapse under their own replication stress.","summary":"ATR is a PI3K-like kinase activated by single-stranded DNA at stalled replication forks; it signals through CHK1 to pause the cell cycle and stabilise forks. Tumours with ATM loss, high replication stress or PARP-inhibitor resistance depend on this alarm, so blocking ATR can make them collapse under their own replication stress. ATR inhibitors (ceralasertib, camonsertib, elimusertib) are in phase 2 and 3, notably ceralasertib with durvalumab in NSCLC after immunotherapy (LATIFY) and in ATM-deficient tumours; ATM loss or mutation is found in about 5 to 10 percent of lung adenocarcinomas. No approval has yet been granted, and myelosuppression limits how freely ATR inhibitors can be combined with chemotherapy or PARP inhibitors. Defining a predictive biomarker beyond ATM loss is the key open problem. For a newcomer: ATR is a DNA-damage alarm that broken-repair tumours cannot afford to lose.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Ataxia_telangiectasia_and_Rad3_related","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ataxia_telangiectasia_and_Rad3_related"}],"tags":["ddr"],"related":[],"cancers":["nsclc","ovarian","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":["ceralasertib"],"companies":["callio-therapeutics","repare-therapeutics"],"institutions":[],"pathways":["ddr","dna-replication-licensing"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"ATR","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA lists ATR among essential proteins and finds the RNA at low tissue specificity; the 1 medicine aimed at it (Ceralasertib) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA ATR: RNA low tissue specificity; no normal tissue stained high. Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Ovarian cancer, Breast cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas ATR tissue","url":"https://www.proteinatlas.org/ENSG00000175054-ATR/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000175054 associations","url":"https://platform.opentargets.org/target/ENSG00000175054/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:882","ensembl":"ENSG00000175054","uniprot":"Q13535","entrez":"545","firstDescribed":1996,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Bentley N.J. et al, EMBO J, 1996, \"The Schizosaccharomyces pombe rad3 checkpoint gene\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8978690/","biology":"PI3K-like kinase activated by single-stranded DNA at stalled forks; signals via CHK1.","whereFound":["Tumours with ATM loss, replication stress, or PARP-inhibitor resistance"],"targetClass":"kinase","prevalence":[{"cancerId":"nsclc","pct":"5-10","measure":"ATM loss/mutation (sensitising context)","source":"https://www.cbioportal.org/study/summary?id=luad_tcga_pan_can_atlas_2018"},{"cancerId":"ovarian","pct":"n/a","measure":"Replication-stress context; no expression threshold","source":"https://en.wikipedia.org/wiki/Ataxia_telangiectasia_and_Rad3_related"}]},"route":"/targets/atr/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"endometrial-p53-abnormal","kind":"cancer","name":"p53-abnormal endometrial cancer, including uterine serous carcinoma","route":"/cancers/endometrial-p53-abnormal/"},{"id":"platinum-sensitive-ovarian-cancer","kind":"cancer","name":"Platinum-sensitive ovarian cancer","route":"/cancers/platinum-sensitive-ovarian-cancer/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"},{"id":"uterine-carcinosarcoma","kind":"cancer","name":"Uterine carcinosarcoma","route":"/cancers/uterine-carcinosarcoma/"}],"drug":[{"id":"ceralasertib","kind":"drug","name":"Ceralasertib","route":"/drugs/ceralasertib/"}],"company":[{"id":"aprea-therapeutics","kind":"company","name":"Aprea Therapeutics","route":"/companies/aprea-therapeutics/"},{"id":"artios-pharma","kind":"company","name":"Artios Pharma","route":"/companies/artios-pharma/"},{"id":"callio-therapeutics","kind":"company","name":"Callio Therapeutics","route":"/companies/callio-therapeutics/"},{"id":"repare-therapeutics","kind":"company","name":"Repare Therapeutics","route":"/companies/repare-therapeutics/"}],"pathway":[{"id":"base-excision-repair-parp","kind":"pathway","name":"Base excision repair, PARP & alkylation damage","route":"/pathways/base-excision-repair-parp/"},{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"},{"id":"dna-replication-licensing","kind":"pathway","name":"DNA replication & origin licensing","route":"/pathways/dna-replication-licensing/"},{"id":"replication-stress","kind":"pathway","name":"DNA replication stress","route":"/pathways/replication-stress/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"swi-snf-chromatin","kind":"pathway","name":"SWI/SNF chromatin remodelling","route":"/pathways/swi-snf-chromatin/"},{"id":"synthetic-lethality-map","kind":"pathway","name":"Synthetic lethality: paired dependencies","route":"/pathways/synthetic-lethality-map/"},{"id":"telomere-maintenance","kind":"pathway","name":"Telomere maintenance & replicative immortality","route":"/pathways/telomere-maintenance/"},{"id":"p53-mdm2-axis","kind":"pathway","name":"The p53 network (guardian of the genome)","route":"/pathways/p53-mdm2-axis/"}],"idea":[{"id":"idea-sclc-subtype-directed","kind":"idea","name":"Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)","route":"/ideas/idea-sclc-subtype-directed/"}],"trial":[{"id":"phoenix","kind":"trial","name":"PHOENIX DDR/Anti-PD-L1","route":"/trials/phoenix/"}],"paper":[{"id":"paper-bao-glioma-stem-cells-radioresistance-nature-2006","kind":"paper","name":"Bao 2006: glioma stem cells resist radiotherapy by activating the DNA damage response","route":"/key-papers/paper-bao-glioma-stem-cells-radioresistance-nature-2006/"},{"id":"paper-wardell-biliary-drivers-germline-j-hepatol-2018","kind":"paper","name":"Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations","route":"/key-papers/paper-wardell-biliary-drivers-germline-j-hepatol-2018/"}],"technology":[{"id":"atr-chk1-inhibitors","kind":"technology","name":"ATR and CHK1 inhibitors","route":"/technologies/atr-chk1-inhibitors/"},{"id":"radionuclide-parp-combination","kind":"technology","name":"Radioligand plus DNA-repair inhibitor combinations","route":"/technologies/radionuclide-parp-combination/"},{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","route":"/technologies/synthetic-lethality-approaches/"}],"person":[{"id":"alan-dandrea","kind":"person","name":"Alan D. D'Andrea","route":"/people/alan-dandrea/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"},{"id":"genome-instability-mutation","kind":"term","name":"Enabling characteristic: genome instability and mutation","route":"/terms/genome-instability-mutation/"}]}}