ArticleCancer chemotherapy and pharmacology2016
Pharmacodynamic modeling of combined chemotherapeutic effects predicts synergistic activity of gemcitabine and trabectedin in pancreatic cancer cells.
Article in Cancer chemotherapy and pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 28 citations in OpenAlex.
- Defining preclinical efficacy with the DNAPK inhibitor AZD7648 in combination with olaparib: a minimal systems pharmacokinetic-pharmacodynamic model.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Systems Pharmacodynamic Model of Combined Gemcitabine and Trabectedin in Pancreatic Cancer Cells. Part I: Effects on Signal Transduction Pathways Related to Tumor GrowthJournal of pharmaceutical sciences · 2024Article
- Systems Pharmacodynamic Model of Combined Gemcitabine and Trabectedin in Pancreatic Cancer Cells. Part II: Cell Cycle, DNA Damage Response, and Apoptosis Pathways.Journal of pharmaceutical sciences · 2024Article
- Model-based assessment of combination therapies - ranking of radiosensitizing agents in oncology.BMC cancer · 2023Article
- Article
- Article
- Exposure-response modeling improves selection of radiation and radiosensitizer combinations.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Synergistic Pharmacodynamic Effects of Gemcitabine and Fibroblast Growth Factor Receptor Inhibitors on Pancreatic Cancer Cell Cycle Kinetics and Proliferation.The Journal of pharmacology and experimental therapeutics · 2021Article
- Pharmacodynamic modeling of synergistic birinapant/paclitaxel interactions in pancreatic cancer cells.BMC cancer · 2020Article
- Mechanistic Multiscale Pharmacokinetic Model for the Anticancer Drug 2',2'-difluorodeoxycytidine (Gemcitabine) in Pancreatic Cancer.Clinical and translational science · 2020Article
- Modeling long-term tumor growth and kill after combinations of radiation and radiosensitizing agents.Cancer chemotherapy and pharmacology · 2019Article
- Assessment of Three-Drug Combination Pharmacodynamic Interactions in Pancreatic Cancer Cells.The AAPS journal · 2018Article
- Model-Based Evaluation of Radiation and Radiosensitizing Agents in Oncology.CPT: pharmacometrics & systems pharmacology · 2018Article
- MEK inhibitors cobimetinib and trametinib, regressed a gemcitabine-resistant pancreatic-cancer patient-derived orthotopic xenograft (PDOX).Oncotarget · 2017Article
- Assessment of non-linear combination effect terms for drug-drug interactions.Journal of pharmacokinetics and pharmacodynamics · 2016Review
- Pharmacodynamic Modeling of Cell Cycle Effects for Gemcitabine and Trabectedin Combinations in Pancreatic Cancer Cells.Frontiers in pharmacology · 2016Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeThis study investigates the combined effects of gemcitabine and trabectedin (ecteinascidin 743) in two pancreatic cancer cell lines and proposes a pharmacodynamic (PD) model to quantify their pharmacological interactions.
methodsEffects of gemcitabine and trabectedin upon the pancreatic cancer cell lines MiaPaCa-2 and BxPC-3 were investigated using cell proliferation assays. Cells were exposed to a range of concentrations of the two drugs, alone and in combination. Viable cell numbers were obtained daily over 5 days. A model incorporating nonlinear cytotoxicity, transit compartments, and an interaction parameter ψ was used to quantify the effects of the individual drugs and combinations.
resultsSimultaneous fitting of temporal cell growth profiles for all drug concentrations provided reasonable cytotoxicity parameter estimates (the cell killing rate constant K max and the sensitivity constant KC50) for each drug. The interaction parameter ψ was estimated as 0.806 for MiaPaCa-2 and 0.843 for BxPC-3 cells, suggesting that the two drugs exert modestly synergistic effects.
conclusionsThe proposed PD model enables quantification of the temporal profiles of drug combinations over a range of concentrations with drug-specific parameters. Based upon these in vitro studies, trabectedin may have augmented benefit in combination with gemcitabine. The PD model may have general relevance for the study of other cytotoxic drug combinations.
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.