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ATR is a DNA-damage alarm kinase. Blocking it makes tumours with broken repair systems collapse under their own replication stress. This dossier gathers the 1 product (0 approved), 8 trials, 7 pathways and 2 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
PI3K-like kinase activated by single-stranded DNA at stalled forks; signals via CHK1.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small-cell lung cancer | 5-10% | ATM loss/mutation (sensitising context) | cBioPortal (TCGA) | |
| Ovarian cancer | n/a | Replication-stress context; no expression threshold | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Phase 3 |
|---|---|
| Small molecule 1 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | A Phase III, Open-label, Randomised, Multicentre Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations, and Whose Disease Has Progressed On or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy: LATIFY | - | ||
| 3 | Active | A Randomized Phase III Trial of Checkpoint Blockade in Lung CancEr Patients in the Adjuvant Setting Based on Pathologic Response Following Neoadjuvant Therapy (CLEAR) | - | ||
| 2 | Active | A Randomised, Open-Label, Phase 2 Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Unresectable or Advanced Melanoma and Primary or Secondary Resistance to PD-(L)1 Inhibition | - | ||
| 2 | Active | An Open-Label, Multi-Drug, Biomarker-Directed, Multi-Centre Phase II Umbrella Study in Patients With Non-Small Cell Lung Cancer, Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (HUDSON). | - | ||
| 2 | Active | A Phase II, Open Label, Randomised, Multi-centre Study to Assess the Safety and Efficacy of Agents Targeting DNA Damage Repair in Combination With Olaparib Versus Olaparib Monotherapy in the Treatment of Metastatic Triple Negative Breast Cancer Patients Stratified by Alterations in Homologous Recombinant Repair (HRR)-Related Genes (Including BRCA1/2) (VIOLETTE). | - | ||
| 2 | Active | A Phase II, Open-label, Multicentre, Non-comparative, Single-arm Local Study of Ceralasertib Plus Durvalumab in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations, and Whose Disease Has Progressed On or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy | - | ||
PHOENIX DDR/Anti-PD-L1 NCT03740893 | 2 | Recruiting | Triple-negative breast cancer with residual disease after neoadjuvant chemotherapy: a pre-surgical window of olaparib, the ATR inhibitor ceralasertib or durvalumab, then post-surgical adjuvant treatment, biomarker-driven, six UK hospitals | - | |
| 2 | Recruiting | Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab/Nab-Paclitaxel: The ATRiBRAVE Trial | - |
Schlafen-11 is required for replication-stress-induced death; its epigenetic silencing confers resistance to TOP1 (and platinum) agents.
Loss of end-protection factors lets BRCA1-deficient cells resect DNA ends and repair by HR.
The DNA damage response is the cell's set of repair crews. Single-strand breaks are patched by PARP; double-strand breaks by BRCA-dependent homologous recombination. Lose one crew and the cell survives; lose both and it dies. That is how PARP inhibitors work.
Which nodes have drugs →Cancers copy their DNA too fast and with broken checkpoints, so replication forks stall and collapse. They survive only by leaning on emergency repair kinases such as ATR, CHK1, and WEE1, which is why blocking those kinases can be selectively lethal.
Which nodes have drugs →A break through both strands of DNA is the most dangerous lesion a cell faces. Two crews compete to fix it: homologous recombination copies the answer from the sister chromosome (accurate, needs BRCA), while end joining simply glues the ends (fast, sloppy). Which crew wins decides whether PARP inhibitors and radiation kill the cell.
Which nodes have drugs →The p53 and RB checkpoints are the cell's brakes. p53 senses damage and stops the cell from copying itself; RB holds the cell at the G1 gate until CDK4/6 unlocks it. Cancers cut these brakes.
Which nodes have drugs →Two genes are synthetically lethal when losing either alone is fine but losing both kills the cell. Cancers that have already lost one (a tumour suppressor you cannot put back) become uniquely dependent on the other, which you can drug. BRCA and PARP was the first proof; a dozen more pairs are now in trials.
Which nodes have drugs →Normal cells can divide only a limited number of times because the protective caps on their chromosomes, telomeres, wear down. About 90% of cancers switch the cap-rebuilding enzyme telomerase back on, often through TERT promoter mutations, and roughly 10% use an alternative lengthening route (ALT), so they divide indefinitely; imetelstat is the first approved telomerase inhibitor.
Which nodes have drugs →p53 is the cell's emergency coordinator: DNA damage, oncogene stress or lack of oxygen switch it on, and it then pauses division, orders repairs, or triggers suicide or permanent retirement, while MDM2 keeps it off in healthy cells. About half of cancers mutate p53 outright, and sarcomas, gliomas, melanomas and retinoblastomas silence it instead by amplifying MDM2 or MDM4.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"ATR" OR ABSTRACT:"ATR") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ATR, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/atr.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/atr.json. Licence CC BY-NC 4.0.