ArticleScientific reports2019
Experimentally-driven mathematical modeling to improve combination targeted and cytotoxic therapy for HER2+ breast cancer.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 54 citations in OpenAlex.
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- Beyond RECIST: mathematical modeling and Bayesian inference reveal the importance of immune parameters in metastatic breast cancer.bioRxiv : the preprint server for biology · 2025Article
- Learning Chemotherapy Drug Action via Universal Physics-Informed Neural Networks.Pharmaceutical research · 2025Article
- Experimentally-driven mathematical model to understand the effects of matrix deprivation in breast cancer metastasis.NPJ systems biology and applications · 2024Article
- Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism.Molecular cancer therapeutics · 2024Article
- Investigating tumor-host response dynamics in preclinical immunotherapy experiments using a stepwise mathematical modeling strategy.Mathematical biosciences · 2023Article
- Mathematical model combined with microdosimetric kinetic model for tumor volume calculation in stereotactic body radiation therapy.Scientific reports · 2023Article
- Multicomponent mathematical model for tumor volume calculation with setup error using single-isocenter stereotactic radiotherapy for multiple brain metastases.Physical and engineering sciences in medicine · 2023Article
- Myeloid-Derived Suppressor-Cell Dynamics Control Outcomes in the Metastatic Niche.Cancer immunology research · 2023Article
- Integration of quantitative methods and mathematical approaches for the modeling of cancer cell proliferation dynamics.American journal of physiology. Cell physiology · 2023Review
- Towards integration of time-resolved confocal microscopy of a 3D in vitro microfluidic platform with a hybrid multiscale model of tumor angiogenesis.PLoS computational biology · 2023Article
- Optimizing combination therapy in a murine model of HER2+ breast cancer.Computer methods in applied mechanics and engineering · 2022Article
- Quantitative system pharmacology as a legitimate approach to examine extrapolation strategies used to support pediatric drug development.CPT: pharmacometrics & systems pharmacology · 2022Review
- Quantification of the growth suppression of HER2+ breast cancer colonies under the effect of trastuzumab and PD-1/PD-L1 inhibitor.Frontiers in oncology · 2022Article
- Effects of Doxorubicin Delivery by Nitrogen-Doped Graphene Quantum Dots on Cancer Cell Growth: Experimental Study and Mathematical Modeling.Nanomaterials (Basel, Switzerland) · 2021Article
- Towards integration ofScientific reports · 2020Article
- QSP-IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno-Oncology Applications.CPT: pharmacometrics & systems pharmacology · 2020Article
- Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models.Cancers · 2020Review
- Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The goal of this study is to experimentally and computationally investigate combination trastuzumab-paclitaxel therapies and identify potential synergistic effects due to sequencing of the therapies with in vitro imaging and mathematical modeling. Longitudinal alterations in cell confluence are reported for an in vitro model of BT474 HER2+ breast cancer cells following various dosages and timings of paclitaxel and trastuzumab combination regimens. Results of combination drug regimens are evaluated for drug interaction relationships based on order, timing, and quantity of dose of the drugs. Altering the order of treatments, with the same total therapeutic dose, provided significant changes in overall cell confluence (p < 0.001). Two mathematical models are introduced that are constrained by the in vitro data to simulate the tumor cell response to the individual therapies. A collective model merging the two individual drug response models was designed to investigate the potential mechanisms of synergy for paclitaxel-trastuzumab combinations. This collective model shows increased synergy for regimens where trastuzumab is administered prior to paclitaxel and suggests trastuzumab accelerates the cytotoxic effects of paclitaxel. The synergy derived from the model is found to be in agreement with the combination index, where both indicate a spectrum of additive and synergistic interactions between the two drugs dependent on their dose order. The combined in vitro results and development of a mathematical model of drug synergy has potential to evaluate and improve standard-of-care combination therapies in cancer.
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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.