Pancreatic ductal adenocarcinoma (PDAC) is an intractable clinical problem, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. Early detection and complete surgical resection offers the best hope for longer survival. Unfortunately, there are currently no suitable biomarkers for early detection. The overall goal of this proposal is to identify novel molecular markers and develop imaging probes for incipient PDAC that would: a) allow much earlier detection of lesions based on molecular signatures, b) provide rational approaches to stratify patients for specific treatments, c) monitor more reliably local recurrence and distant metastases, d) serve as response biomarkers or """"""""surrogates"""""""" for new targeted therapies, and e) differentiate benign tumors from malignant PDAC. Our group has been actively involved in the development of techniques and molecular imaging agents that enable earlier detection of primary cancer, metastatic spread, and early evaluation of therapeutic efficacy by molecular imaging. We have also developed genetically engineered mouse PDAC models and primary human orthotopic xenograft systems for preclinical early detection and therapeutic studies. In an extension of our previous work, we will use previously optimized phage display technology, proteomics methods, and clinically relevant nanoparticles to 1) screen against known PDAC targets, and 2) identify novel targets in PDAC tissues, and in pre-invasive precursor lesions (PanINs). Our goals are to develop targeted agents for the non-invasive imaging of the tumor and its microenvironment and to identify novel biomarkers. We will test the novel imaging agents in vivo using our relevant PDAC mouse models and orthotopic human xenografts.
The overall goal of this proposal is to develop new imaging approaches for the early detection of pancreatic cancer. We will do this by utilizing recently developed mouse models that recapitulate the genetics of human disease. Sophisticated chemical biology approaches will be used to find novel tags that will allow us to pinpoint the earliest forms of cancer. We hope to use these tags in conjunction with commonly used imaging approaches such as MRI or endoscopic detection.
|Konkalmatt, Prasad R; Deng, Defeng; Thomas, Stephanie et al. (2013) Plectin-1 Targeted AAV Vector for the Molecular Imaging of Pancreatic Cancer. Front Oncol 3:84|
|Shin, Soo J; Smith, Jeffrey A; Rezniczek, GÃ¼nther A et al. (2013) Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer. Proc Natl Acad Sci U S A 110:19414-9|
|Beech, Jaymes R; Shin, Soo J; Smith, Jeffrey A et al. (2013) Mechanisms for targeted delivery of nanoparticles in cancer. Curr Pharm Des 19:6560-74|
|Shin, Soo J; Beech, Jaymes R; Kelly, Kimberly A (2013) Targeted nanoparticles in imaging: paving the way for personalized medicine in the battle against cancer. Integr Biol (Camb) 5:29-42|
|Ghosh, Debadyuti; Lee, Youjin; Thomas, Stephanie et al. (2012) M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer. Nat Nanotechnol 7:677-82|
|Seaman, Marc E; Peirce, Shayn M; Kelly, Kimberly (2011) Rapid analysis of vessel elements (RAVE): a tool for studying physiologic, pathologic and tumor angiogenesis. PLoS One 6:e20807|
|Bausch, Dirk; Thomas, Stephanie; Mino-Kenudson, Mari et al. (2011) Plectin-1 as a novel biomarker for pancreatic cancer. Clin Cancer Res 17:302-9|
|Reynolds, Fred; Kelly, Kimberly A (2011) Techniques for molecular imaging probe design. Mol Imaging 10:407-19|
|Thomas, Stephanie; Waterman, Peter; Chen, Suelin et al. (2011) Development of Secreted Protein and Acidic and Rich in Cysteine (SPARC) Targeted Nanoparticles for the Prognostic Molecular Imaging of Metastatic Prostate Cancer. J Nanomed Nanotechnol 2:|
|Seaman, Marc E; Contino, Gianmarco; Bardeesy, Nabeel et al. (2010) Molecular imaging agents: impact on diagnosis and therapeutics in oncology. Expert Rev Mol Med 12:e20|
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