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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.
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.
In plain words · ATR is a DNA-damage alarm kinase. Blocking it makes tumours with broken repair systems collapse under their own replication stress.
ATR is a DNA-damage alarm kinase. Blocking it makes tumours with broken repair systems collapse under their own replication stress.
PI3K-like kinase activated by single-stranded DNA at stalled forks; signals via CHK1.
1 product aims at ATR: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
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.)
Sources: Human Protein Atlas ATR tissue; Open Targets ENSG00000175054 associations
First described 1996. Earliest sequence paper UniProt cites for the protein: Bentley N.J. et al, EMBO J, 1996, "The Schizosaccharomyces pombe rad3 checkpoint gene". Source.
PI3K-like kinase activated by single-stranded DNA at stalled forks; signals via CHK1.
RNA: low tissue specificity, detected in many normal tissues.
No normal tissue stained high.
No cancer sample stained medium or high.
HPA ATR tissue · HPA ATR pathology · HPA protein class: Essential proteins
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| 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.
Ceralasertib is an experimental small-molecule drug from AstraZeneca in phase 3 trials for non-small-cell lung cancer, melanoma and triple-negative breast cancer, aimed at ATR.
The germline finding is the practical lesson: a meaningful minority of biliary cancer patients carry inherited repair-gene mutations that matter for PARP inhibitor eligibility and for their relatives, which argues for germline testing alongside tumour sequencing.
This paper connected the cancer stem cell idea to a clinical problem, the near-universal recurrence of glioblastoma after radiotherapy, and gave a mechanism and a drug target. It is part of the rationale for combining radiotherapy with DNA damage response inhibitors now in trials.
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.
Shares DNA replication stress, Uterine carcinosarcoma, The p53 network (guardian of the genome), p53-abnormal endometrial cancer, including uterine serous carcinoma and the tag ddr.
Shares Alan D. D'Andrea, Radioligand plus DNA-repair inhibitor combinations, Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed), Enabling characteristic: genome instability and mutation.
Shares Base excision repair, PARP & alkylation damage, DNA replication stress, Synthetic lethality: paired dependencies, Synthetic lethality approaches.
Shares DNA replication stress, DNA damage response & homologous recombination, Checkpoint (two meanings), Small-cell lung cancer.
Shares Enabling characteristic: genome instability and mutation, Synthetic lethality: paired dependencies, Platinum-sensitive ovarian cancer, DNA damage response & homologous recombination.
Shares Aprea Therapeutics, The p53 network (guardian of the genome), p53 / RB / cell-cycle checkpoint.
Shares Synthetic lethality: paired dependencies, DNA damage response & homologous recombination, Double-strand break repair: HR versus end joining, Ovarian cancer.
Shares Base excision repair, PARP & alkylation damage, Synthetic lethality: paired dependencies, Double-strand break repair: HR versus end joining.