Experimentally-driven mathematical modeling to improve combination targeted and cytotoxic therapy for HER2+ breast cancer

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 repo...

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Bibliographic Details
Published in:Scientific reports 2019-09, Vol.9 (1), p.12830-12, Article 12830
Main Authors: Jarrett, Angela M, Shah, Alay, Bloom, Meghan J, McKenna, Matthew T, Hormuth, 2nd, David A, Yankeelov, Thomas E, Sorace, Anna G
Format: Article
Language:English
Subjects:
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Breast cancer
Breast Neoplasms - drug therapy
Calibration
Cancer therapies
Cell Death - drug effects
Cell Line, Tumor
Computer Simulation
Cytotoxicity
Dosage
Drug dosages
Drug interaction
ErbB-2 protein
Female
Humans
Mathematical models
Models, Biological
Monoclonal antibodies
Paclitaxel
Paclitaxel - pharmacology
Paclitaxel - therapeutic use
Receptor, ErbB-2 - metabolism
Targeted cancer therapy
Trastuzumab
Trastuzumab - pharmacology
Trastuzumab - therapeutic use
Treatment Outcome
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Summary: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 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-49073-5