ArticleCPT: pharmacometrics & systems pharmacology2014
Multiscale design of cell-type-specific pharmacokinetic/pharmacodynamic models for personalized medicine: application to temozolomide in brain tumors.
Article in CPT: pharmacometrics & systems pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- A Randomized, Open-Label, Two-Way Crossover, Single-Dose Bioequivalence Study of Temozolomide 200 mg/mDrugs in R&D · 2017Trial
- Experimentally calibrated multiscale model predicts schedule dependent drug combination effects.NPJ systems biology and applications · 2026Article
- Gold Nanoparticle-Based Precision Medicine Strategies for Glioblastoma: Current Biomedical Applications and Future Outlook.Molecules (Basel, Switzerland) · 2026Review
- A pharmacokinetic-pharmacodynamic/toxicodynamic model framework for PARP inhibitor combination therapy with DNA-damaging chemotherapeutics.Cancer chemotherapy and pharmacology · 2026Article
- BRD2 bromodomain-mediated regulation of cell state plasticity modulates therapy response in glioblastoma.Neuro-oncology · 2025Article
- Temozolomide-Derived AIC Is Incorporated into Purine Synthesis in Glioblastoma.Chemical research in toxicology · 2025Article
- Review
- Circadian regulation of MGMT expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma.Journal of neuro-oncology · 2024Article
- Article
- Nitric Oxide Prevents Glioblastoma Stem Cells' Expansion and Induces Temozolomide Sensitization.International journal of molecular sciences · 2023Article
- Cell state-directed therapy - epigenetic modulation of gene transcription demonstrated with a quantitative systems pharmacology model of temozolomide.CPT: pharmacometrics & systems pharmacology · 2023Article
- Mathematical modeling of regulatory networks of intracellular processes - Aims and selected methods.Computational and structural biotechnology journal · 2023Review
- Review
- A randomized feasibility study evaluating temozolomide circadian medicine in patients with glioma.Neuro-oncology practice · 2022Article
- Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy.BioMed research international · 2022Article
- Epigenetic instability may alter cell state transitions and anticancer drug resistance.PLoS computational biology · 2021Article
- Hybrid physiologically-based pharmacokinetic model for remdesivir: Application to SARS-CoV-2.Clinical and translational science · 2021Article
- Mitigating temozolomide resistance in glioblastoma via DNA damage-repair inhibition.Journal of the Royal Society, Interface · 2020Article
- Sex-, feeding-, and circadian time-dependency of P-glycoprotein expression and activity - implications for mechanistic pharmacokinetics modeling.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Optimizing anticancer therapeutics needs to account for variable drug responses in heterogeneous cell populations within the tumor as well as in organs of toxicity. To address cell heterogeneity, we propose a multiscale modeling approach-from in vitro to preclinical and clinical studies-to develop cell-type-specific pharmacokinetic-pharmacodynamic (PK-PD) models. A physiologically based mechanistic modeling approach integrating data from aqueous solutions, U87 glioma cells, mice, and cancer patients was utilized to characterize the brain disposition of temozolomide (TMZ), the cornerstone of chemotherapy against glioblastoma multiforme. The final model represented intracellular normal brain and brain tumor compartments in which TMZ pH-dependent conversion to the DNA-alkylating species leads to the formation of DNA adducts that serve as an entry point for a PD model. This multiscale protocol can be extended to account for TMZ PK-PD in different cell populations, thus providing a critical tool to personalize TMZ-based chemotherapy on a cell-type-specific basis.
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.