@article{f826ecdd73b141f2bd1ed1724b916378,
title = "A murine preclinical syngeneic transplantation model for breast cancer precision medicine",
abstract = "We previously demonstrated that altered activity of lysophosphatidic acid in murine mammary glands promotes tumorigenesis. We have now established and characterized a heterogeneous collection of mouse-derived syngeneic transplants (MDSTs) as preclinical platforms for the assessment of personalized pharmacological therapies. Detailed molecular and phenotypic analyses revealed that MDSTs are the most heterogeneous group of genetically engineered mouse models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor, correlated with RAS/MAPK signaling activity, as expected from studies in xenografts and clinical trials providing validation of the utility of the model. Sensitivity of MDSTs to talazoparib, a poly(adenosine 5′-diphosphate–ribose) polymerase (PARP) inhibitor, was predicted by PARP1 protein levels and by a new PARP sensitivity predictor (PSP) score developed from integrated analysis of drug sensitivity data of human cell lines. PSP score–based classification of The Cancer Genome Atlas breast cancer suggested that a subset of patients with limited therapeutic options would be expected to benefit from PARP-targeted drugs. These results indicate that MDSTs are useful models for studies of targeted therapies, and propose novel potential biomarkers for identification of breast cancer patients likely to benefit from personalized pharmacological treatments.",
author = "Lorenzo Federico and Zechen Chong and Dong Zhang and McGrail, {Daniel J.} and Wei Zhao and Jeong, {Kang Jin} and Vellano, {Christopher P.} and Zhenlin Ju and Mihai Gagea and Shuying Liu and Shreya Mitra and Dennison, {Jennifer B.} and Lorenzi, {Philip L.} and Robert Cardnell and Lixia Diao and Jing Wang and Yiling Lu and Byers, {Lauren A.} and Perou, {Charles M.} and Lin, {Shiaw Yih} and Mills, {Gordon B.}",
note = "Funding Information: We would like to thank the MD Anderson Cancer Center RPPA Core Facility [National Cancer Institute (NCI) grant no. CA16672] for processing all samples and analyzing protein expression data. We also appreciate work done by the SU2C program through the SU2C Translational Research Grant, a program of the Entertainment Industry Foundation (SU2C-AACR-DT0209), to provide trametinib (GSK1120212) and talazoparib (BMN-673) compounds for in vivo efficacy studies. We also extend special thanks to D. Wienke, K. Schiemann (medicinal chemistry), and A. Zimmermann (in vivo pharmacology) of Merck KGaA for providing MSC2285264 (patent no. WO2011044978) to test the effects of ATX inhibition in our models. This work was supported by Breast Cancer Research Foundation (BCRF) grant no. CV11121387 and in part by NCI grant nos. CA16672 and RO1-CA148761, NCI Breast SPORE (Specialized Program of Research Excellence) program grant no. P50-CA58223-09A, and Cancer Prevention Research Institute of Texas grant no. RP130397. Publisher Copyright: {\textcopyright} 2017 The Authors.",
year = "2017",
month = apr,
doi = "10.1126/sciadv.1600957",
language = "English (US)",
volume = "3",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "4",
}