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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA137071-05
Application #
8298483
Study Section
Special Emphasis Panel (ZRG1-MEDI-A (09))
Program Officer
Menkens, Anne E
Project Start
2008-09-17
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$248,508
Indirect Cost
$49,142
Name
University of Virginia
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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