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 0 products (0 approved), 0 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.
Biology
PI3K-like kinase activated by single-stranded DNA at stalled forks; signals via CHK1.
- Tumours with ATM loss, replication stress, or PARP-inhibitor resistance
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| 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.
Products by modality and phase
Browse products →No product in the corpus is aimed at this target yet.
Trials
Evidence ranking →No trial in the corpus names this target or one of its products.
Resistance routes that involve this target
Unaddressed routes →Schlafen-11 is required for replication-stress-induced death; its epigenetic silencing confers resistance to TOP1 (and platinum) agents.
- ATR/CHK1 inhibitors re-sensitise SLFN11-low cells preclinically
- EZH2 inhibition to restore SLFN11 (preclinical)
Loss of end-protection factors lets BRCA1-deficient cells resect DNA ends and repair by HR.
- ATR inhibitors; POLQ inhibitors (trials)
Pathways where it is a node
Pathway-to-drug matrix →- DNA damage response & homologous recombinationNode: ATR / CHK1 · 3 druggable nodes
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 → - DNA replication stressNode: ATR → CHK1 · 4 druggable nodes
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 → - Double-strand break repair: HR versus end joiningNode: MRN → ATM → CHK2 · 4 druggable nodes
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 → - p53 / RB / cell-cycle checkpointNode: ATM / ATR · 4 druggable nodes
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 → - Synthetic lethality: paired dependenciesNode: → ATR · 7 druggable nodes
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 → - Telomere maintenance & replicative immortalityNode: ATR dependence (ALT) · 1 druggable nodes
Normal cells can divide only so many times because the protective caps on their chromosomes, telomeres, wear down. Cancers switch the cap-rebuilding enzyme telomerase back on, or find another way (ALT), so they can divide forever.
Which nodes have drugs → - The p53 network (guardian of the genome)Node: DNA damage (ATM/ATR) · 4 druggable nodes
p53 is the cell's emergency coordinator. Damage, oncogene stress, or lack of oxygen switch it on; it then pauses division, orders repairs, or triggers suicide or permanent retirement. MDM2 keeps it switched off in healthy cells. Half of all cancers break p53 outright; many of the rest over-produce MDM2.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →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.
Export
The dossier as machine-readable 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 4.0.