ArticleScientific reports2015
Bridging the gap between in vitro and in vivo: Dose and schedule predictions for the ATR inhibitor AZD6738.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 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
30 citing papers in PubMed, 69 citations in OpenAlex.
- Model based analysis of the heterogeneity in the tumour size dynamics differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma.Cancer chemotherapy and pharmacology · 2018Trial
- PK-Informed Microphysiological Systems: From Dynamic Dosing to Quantitative In Vitro-In Vivo Translation.Pharmaceutics · 2026Review
- A hybrid PKPD agent-based model of the tumour immune interaction: effects of anti-cancer combination therapy.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Targeting the DNA damage response prevents regrowth of colorectal peritoneal metastasis-derived organoids following treatment with mitomycin C.British journal of cancer · 2026Article
- Defining preclinical efficacy with the DNAPK inhibitor AZD7648 in combination with olaparib: a minimal systems pharmacokinetic-pharmacodynamic model.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- An integrated quantitative systems pharmacology virtual population approach for calibration with oncology efficacy endpoints.CPT: pharmacometrics & systems pharmacology · 2025Article
- DNA-PK inhibition extends the therapeutic effects of Top2 poisoning to non-proliferating cells, increasing activity at a cost.Scientific reports · 2023Article
- Pharmacokinetic/Pharmacodynamic Analysis of Savolitinib plus Osimertinib in an EGFR Mutation-Positive, MET-Amplified Non-Small Cell Lung Cancer Model.Molecular cancer therapeutics · 2023Article
- AZD6738 promotes the tumor suppressive effects of trifluridine in colorectal cancer cells.Oncology reports · 2023Article
- RNA therapeutics in the clinic.Bioengineering & translational medicine · 2023Review
- The Application of ATR Kinase Inhibitor AZD6738 in Combination with Radiotherapy for the Treatment of Melanoma.Journal of biomedical physics & engineering · 2022Article
- Exposure-response modeling improves selection of radiation and radiosensitizer combinations.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- How translational modeling in oncology needs to get the mechanism just right.Clinical and translational science · 2022Review
- Enhanced ASGR2 by microplastic exposure leads to resistance to therapy in gastric cancer.Theranostics · 2022Article
- Review
- Targeting Cellular DNA Damage Responses in Cancer: An In Vitro-Calibrated Agent-Based Model Simulating Monolayer and Spheroid Treatment Responses to ATR-Inhibiting Drugs.Bulletin of mathematical biology · 2021Article
- Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations.NPJ breast cancer · 2021Article
- Plant-Derived Anticancer Compounds as New Perspectives in Drug Discovery and Alternative Therapy.Molecules (Basel, Switzerland) · 2021Review
- Synergism of AZD6738, an ATR Inhibitor, in Combination with Belotecan, a Camptothecin Analogue, in Chemotherapy-Resistant Ovarian Cancer.International journal of molecular sciences · 2021Article
- Does In Vitro Potency Predict Clinically Efficacious Concentrations?Clinical pharmacology and therapeutics · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the therapeutic effect of drug dose and scheduling is critical to inform the design and implementation of clinical trials. The increasing complexity of both mono, and particularly combination therapies presents a substantial challenge in the clinical stages of drug development for oncology. Using a systems pharmacology approach, we have extended an existing PK-PD model of tumor growth with a mechanistic model of the cell cycle, enabling simulation of mono and combination treatment with the ATR inhibitor AZD6738 and ionizing radiation. Using AZD6738, we have developed multi-parametric cell based assays measuring DNA damage and cell cycle transition, providing quantitative data suitable for model calibration. Our in vitro calibrated cell cycle model is predictive of tumor growth observed in in vivo mouse xenograft studies. The model is being used for phase I clinical trial designs for AZD6738, with the aim of improving patient care through quantitative dose and scheduling prediction.
Indexed as
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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.