PROJECT OVERVIEW This project will focus on the application of nanotechnology to the unique problems of pancreatic adenocarcinoma (PAC). Unlike what is observed in other solid tumors, pancreafic cancer cells exist as foci embedded in an abundant dense hypovascular fibrofic stroma. Development of this dense stroma begins with eariy premalignant disease (pancreatic intraepithelial neoplasia (PanIN)) and continues through tumor progression. A primary goal of this project will be to develop nanotechnologies that can either penetrate or accumulate in the abundant stroma that characterizes pancreafic cancer. The ability to specifically deliver therapies to the pancreafic tumors will also allow the use of therapies directed at appropriate targets in individual patients, opening the door to individualized therapies. Unfortunately, the current preclinical tumor models for PAC do not develop stroma and thus do not accurately represent the microenvironment found in the human disease. Recentiy, we have developed novel preclinical mouse models, both xenografts and genetic, which accurately mimic this fibrofic microenvironment. We will use these novel and unique model systems to develop optimized nanotechnologies that target and accumulate within pancreafic stromal networks for therapy. Imaging, and prevenfion of PAC. Thus, we will effectively turn what was a barrier to therapeutic delivery into a reservoir for preventive and therapeutic agents. Alternatively, we will suppress the biological activity of the stromal cells to prevent cancer progression or to render the cancer more amenable to cancer cell directed therapies. Together these studies will, for the first fime, ufilize nanocarriers to penetrate the barrier surrounding pancreafic tumors to achieve clinically significant goals.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-GRB-S)
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University of Texas Health Science Center Houston
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Seo, Hyeonglim; Choi, Ikjang; Whiting, Nicholas et al. (2018) Hyperpolarized Porous Silicon Nanoparticles: Potential Theragnostic Material for 29 Si Magnetic Resonance Imaging. Chemphyschem 19:2143-2147
Koay, Eugene J; Lee, Yeonju; Cristini, Vittorio et al. (2018) A Visually Apparent and Quantifiable CT Imaging Feature Identifies Biophysical Subtypes of Pancreatic Ductal Adenocarcinoma. Clin Cancer Res 24:5883-5894
Zacharias, Niki; Lee, Jaehyuk; Ramachandran, Sumankalai et al. (2018) Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Alters Hyperpolarized Pyruvate to Lactate Conversion and Lactate Levels In Vivo. Mol Imaging Biol :
Hövener, Jan-Bernd; Pravdivtsev, Andrey N; Kidd, Bryce et al. (2018) Parahydrogen-Based Hyperpolarization for Biomedicine. Angew Chem Int Ed Engl 57:11140-11162
Mai, Junhua; Li, Xin; Zhang, Guodong et al. (2018) DNA Thioaptamer with Homing Specificity to Lymphoma Bone Marrow Involvement. Mol Pharm 15:1814-1825
Kojic, M; Milosevic, M; Kojic, N et al. (2018) Mass release curves as the constitutive curves for modeling diffusive transport within biological tissue. Comput Biol Med 92:156-167
Zhou, Jinhua; Alfraidi, Albandri; Zhang, Shu et al. (2017) A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel. Clin Cancer Res 23:1945-1954
Wolfram, Joy; Nizzero, Sara; Liu, Haoran et al. (2017) A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery. Sci Rep 7:13738
Borsoi, Carlotta; Leonard, Fransisca; Lee, Yeonju et al. (2017) Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma. Cancer Lett 403:296-304
Zacharias, Niki Marie; McCullough, Christopher; Shanmugavelandy, Sriram et al. (2017) Metabolic Differences in Glutamine Utilization Lead to Metabolic Vulnerabilities in Prostate Cancer. Sci Rep 7:16159

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