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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 BRAF-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. Cancer Res; 77(19); 5409-18. ©2017 AACR.

Original publication

DOI

10.1158/0008-5472.CAN-17-0835

Type

Journal article

Journal

Cancer Res

Publication Date

01/10/2017

Volume

77

Pages

5409 - 5418

Keywords

Animals, Drug Resistance, Neoplasm, Focal Adhesion Kinase 1, Humans, Indoles, Melanoma, Mice, Models, Theoretical, Molecular Targeted Therapy, Proto-Oncogene Proteins B-raf, Stromal Cells, Sulfonamides, Tumor Cells, Cultured, Tumor Microenvironment, Xenograft Model Antitumor Assays