ArticleJCI insight2023
The schedule of ATR inhibitor AZD6738 can potentiate or abolish antitumor immune responses to radiotherapy.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 32 citations in OpenAlex.
- Trial
- Resolution and Quantitation of Ribonucleosides and Deoxyribonucleosides in Digested Genomic DNA by UHPLC-MS/MS.Biomedical chromatography : BMC · 2026Article
- ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.NPJ precision oncology · 2026Article
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Transient ATR inhibition following ionizing radiation enhances immune-mediated antitumor response and survival.bioRxiv : the preprint server for biology · 2026Article
- ATR kinase inhibitors induce mitochondrial fission in CD8bioRxiv : the preprint server for biology · 2026Article
- Therapeutic scheduling of WEE1 inhibition preserves T cell function and promotes immune control of HPVbioRxiv : the preprint server for biology · 2026Article
- Article
- Review
- Pathway for the Development of ATR Inhibitors in Pediatric Malignancies: An ACCELERATE Multistakeholder Analysis.JCO precision oncology · 2026Review
- Promising Targets and Drugs for Improving Head and Neck Cancer Response to Radiotherapy.Current pharmaceutical design · 2026Review
- Targeting ATR offers multifaceted treatment strategies involving RAD51-mediated compensatory DNA repair in bladder cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Article
- Targeting DNA Damage Response and Immune Crosstalk in Cancer: Mechanistic Insights and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Tumor control and immune activation through palliative irradiation and ATR inhibition, PATRIOT Part C: a phase Ib trial.Nature communications · 2025Article
- PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.Cell death discovery · 2025Article
- Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).Cancer chemotherapy and pharmacology · 2025Article
- Synthetic reprogramming of tumor cell fate for modulating radiotherapy-induced dynamic responses: perspectives on radiosensitizing and immunoregulatory effects.Theranostics · 2025Review
- ATR inhibition radiosensitizes cells through augmented DNA damage and G2 cell cycle arrest abrogation.JCI insight · 2024Article
- Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy.Nature communications · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Inhibitors of the DNA damage signaling kinase ATR increase tumor cell killing by chemotherapies that target DNA replication forks but also kill rapidly proliferating immune cells including activated T cells. Nevertheless, ATR inhibitor (ATRi) and radiotherapy (RT) can be combined to generate CD8+ T cell-dependent antitumor responses in mouse models. To determine the optimal schedule of ATRi and RT, we determined the impact of short-course versus prolonged daily treatment with AZD6738 (ATRi) on responses to RT (days 1-2). Short-course ATRi (days 1-3) plus RT caused expansion of tumor antigen-specific, effector CD8+ T cells in the tumor-draining lymph node (DLN) at 1 week after RT. This was preceded by acute decreases in proliferating tumor-infiltrating and peripheral T cells and a rapid proliferative rebound after ATRi cessation, increased inflammatory signaling (IFN-β, chemokines, particularly CXCL10) in tumors, and an accumulation of inflammatory cells in the DLN. In contrast, prolonged ATRi (days 1-9) prevented the expansion of tumor antigen-specific, effector CD8+ T cells in the DLN, and entirely abolished the therapeutic benefit of short-course ATRi with RT and anti-PD-L1. Our data argue that ATRi cessation is essential to allow CD8+ T cell responses to both RT and immune checkpoint inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.