A Cell-Based Approach to Early Pancreatic Cancer Detection
Abstract
One of the factors making pancreatic cancer so difficult to treat is its proclivity to spread early. In most patients, the diagnosis of pancreatic cancer is made after there has been metastasis to distant sites in the body, when treatment options are quite limited. Work in the field over the past decade has greatly advanced our understanding of how pancreatic cancers develop in the first place -- the genes and molecular signaling pathways that promote tumor growth -- but comparatively little is known about the mechanisms by which pancreatic cancer metastasizes. An emerging area in cancer biology has been the use of "circulating tumor cells" (or CTCs) for the diagnosis and management of cancer. These cells are released into the bloodstream from a primary tumor, where they can be detected and studied. CTCs provide a way of scrutinizing the biology of tumor -- knowing whether there are mutations that might make a tumor particularly susceptible to certain drugs, for example -- without the need to perform an invasive biopsy. This technology is particularly well suited to pancreatic cancer because the pancreas location deep inside the abdomen makes it difficult to access for tissue diagnoses. Nevertheless, there are several significant technical hurdles that impede our ability to apply this technique widely, including the fact that many or most tumor cells lose the characteristics that allow them to be readily detected in the blood. Using a mouse model of pancreatic cancer that allows us to tag and track cells as they enter the bloodstream, we have been able to see when cells first escape from the pancreas and spread throughout the body. Our finding, consistent with the longstanding clinical observation that this cancer type spreads early, is that pancreatic cells enter the bloodstream at a very early stage in tumor progression -- a stage we would have previously labeled "pre-cancerous." Hence, the presence of pancreatic cells in the circulation (what we term "circulating epithelial cells" or CECs) before a tumor can be detected by CT (computed tomography) scan or ultrasound, provides a rationale for an approach to early detection. The current proposal builds upon these observations to develop a specific, sensitive, and convenient diagnostic test for pancreatic cancer. Our approach exploits the fact that pancreatic cells are released into the blood at the initial stages of cancer. We will leverage the skills of our team -- with expertise in pancreatic cancer, bioengineering, and circulating tumor cell biology -- to detect these cells and their molecular cargo. The initial stages of the project will optimize techniques for isolating or enriching these cells in patients known to have cancer, but this study will lay the groundwork for the development of a screening test for high-risk individuals and eventually the general population. By the conclusion of the grant term, we hope to have a prototype clinical assay in hand whereby a blood sample taken from a pancreatic cancer patient is rapidly processed, pancreas-derived cells are detected and analyzed, and the results used for clinical decision-making.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510457
Entities
People
- Ben Z Stanger
Organizations
- United States Army
- University of Pennsylvania