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)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Health Science Center Houston
United States
Zip Code
Ornelas, Argentina; McCullough, Christopher R; Lu, Zhen et al. (2016) Induction of autophagy by ARHI (DIRAS3) alters fundamental metabolic pathways in ovarian cancer models. BMC Cancer 16:824
Zacharias, Niki M; McCullough, Christopher R; Wagner, Shawn et al. (2016) Towards Real-time Metabolic Profiling of Cancer with Hyperpolarized Succinate. J Mol Imaging Dyn 6:
Hatakeyama, Hiroto; Wu, Sherry Y; Mangala, Lingegowda S et al. (2016) Assessment of In Vivo siRNA Delivery in Cancer Mouse Models. Methods Mol Biol 1402:189-97
Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P et al. (2016) Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release. Proc Natl Acad Sci U S A 113:1877-82
Tasciotti, Ennio; Cabrera, Fernando J; Evangelopoulos, Michael et al. (2016) The Emerging Role of Nanotechnology in Cell and Organ Transplantation. Transplantation 100:1629-38
Au Yeung, Chi Lam; Co, Ngai-Na; Tsuruga, Tetsushi et al. (2016) Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat Commun 7:11150
Zhou, Min; Melancon, Marites; Stafford, R Jason et al. (2016) Precision Nanomedicine Using Dual PET and MR Temperature Imaging-Guided Photothermal Therapy. J Nucl Med 57:1778-1783
Van Roosbroeck, Katrien; Fanini, Francesca; Setoyama, Tetsuro et al. (2016) Combining anti-miR-155 with chemotherapy for the treatment of lung cancers. Clin Cancer Res :
Mi, Yu; Wolfram, Joy; Mu, Chaofeng et al. (2016) Enzyme-responsive multistage vector for drug delivery to tumor tissue. Pharmacol Res 113:92-99
Rupaimoole, R; Ivan, C; Yang, D et al. (2016) Hypoxia-upregulated microRNA-630 targets Dicer, leading to increased tumor progression. Oncogene 35:4312-20

Showing the most recent 10 out of 308 publications