Integrating models to quantify environment-mediated drug resistance
Abstract
Drug resistance is the single most important driver of cancer treatment failure for modern targeted therapies, and the dialog between tumor and stroma has been shown to modulate the response to molecularly targeted therapies through proliferative and survival signaling. In this work, we investigate interactions between a growing tumor and its surrounding stroma and their role in facilitating the emergence of drug resistance. We used mathematical modeling as a theoretical framework to bridge between experimental models and scales, with the aim of separating intrinsic and extrinsic components of resistance in -mutated melanoma; the model describes tumor-stroma dynamics both with and without treatment. Integration of experimental data into our model revealed significant variation in either the intensity of stromal promotion or intrinsic tissue carrying capacity across animal replicates. .
Journal details
Journal Cancer Research
Volume 77
Issue number 19
Pages 5409-5418
Available online
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Publisher website (DOI) 10.1158/0008-5472.can-17-0835
Europe PubMed Central 28754669
Pubmed 28754669
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