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Talent & Technology

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Pancreatic

Canary’s pancreatic cancer research program is focused on developing diagnostics with a high degree of sensitivity and specificity to detect lethal pancreatic cancers at an early stage.

According to the Centers for Disease Control, pancreatic cancer is a “top ten” cancer killer, causing over 259,000 deaths per year worldwide, and in the United States, it is the fifth leading cause of cancer-related mortality. Pancreatic cancer accounts for about 3% of all cancers in the US, and accounts for about 7% of cancer deaths (American Cancer Society).

A diagnosis of pancreatic cancer often carries a poor prognosis because patients are asymptomatic until advanced stages. The vast majority of cases of pancreatic cancer are diagnosed when cancer has spread to adjacent tissues or widely beyond the site of origin. Consequently, the likelihood of a cure through surgical removal is extremely low. As with many other lethal cancers, early detection of pancreatic cancer promises to save many lives, as chances of survival are greatest when cancer is diagnosed at a stage when it is still confined to the pancreas.

Pancreatic cancer is commonly diagnosed in its later stages, leaving patients at the point where they are no longer surgical candidates. Dr. Dawson is involved in developing ways to diagnose this type of disease earlier through pathological testing.

Team

Members of the team include physicians who focus on pancreatic cancer, imaging experts, and researchers who focus on development of biomarkers for early detection of disease.

  • Teri Brentnall, M.D., University of Washington
  • Ru Chen, Ph.D., University of Washington
  • David Dawson, M.D., Ph.D., University of California at Los Angeles
  • Tim Donahue, M.D., University of California at Los Angeles
  • Kim Kelly, Ph.D., University of Virginia
  • Parag Mallick, Ph.D., Stanford University
  • Brad Nelson, Ph.D., British Columbia Cancer Agency
  • Sheng Pan, Ph.D., University of Washington

Progress and Results

Early Detection Biomarkers

The blood biomarker CA-19-9 is currently the only clinically used blood test for pancreatic cancer, but it lacks the sensitivity and specificity needed to detect early-stage pancreatic cancer. The Canary team is working to develop more accurate blood-based or saliva-based biomarkers.

The team is pursuing Multiple Reaction Monitoring (MRM), in which proteins of interest are directly measured in the plasma, without the need for antibodies. This project is designed to alleviate the bottleneck of antibody development in the efforts to bring lab discoveries to the clinic.

In addition to protein biomarkers in the blood, the team is also pursuing alternative biomarkers such as cancer-specific microRNAs in the saliva of patients with pancreatic diseases.

Molecular Imaging for Pancreatic Cancer

The pancreatic cancer team is pursuing development of sensitive, specific, and low-impact imaging for early detection of pancreatic cancer.

Current imaging techniques such as CT, ultrasound, and MRI are not reliable for early detection of pancreatic cancer or discrimination of cancer vs. diseases such as chronic pancreatitis. Development of new imaging agents to discriminate pancreatic cancer compared to benign diseases, as well as small early-stage pancreatic tumors, is critically needed.

The team has demonstrated the ability to detect small pancreatic cancers, less than 1 millimeter in size, using ultrasound with targeted microbubble technology in mouse models of pancreatic cancer. The team has also discovered a new candidate biomarker for pancreatic cancer imaging, Thymocyte Differentiation Antigen 1 (Thy1). Thy1 is expressed in vascular endothelial cells early in pancreatic cancer development. Ultrasound imaging with Thy1-targeted microbubbles in mouse models of pancreatic cancer shows promise, as the imaging agent visualizes pancreatic cancer and not benign disease. Thy1 is also being developed for other imaging modalities, including photoacoustic imaging.

https://youtu.be/PsVjRvuKZCw?list=PLPVm7HiUiQx55YEe81bHDG26O-9nM3ivo

Where Canary Science is Happening 

  • University of Washington, Seattle, Washington
  • British Columbia Cancer Agency, Victoria, British Columbia
  • Stanford University, Stanford, California
  • University of Virginia, Charlottesville, Virginia
  • University of California, Los Angeles, California

Canary Supported Pancreatic Cancer Papers

Pysz, M.A., et al. Vascular Endothelial Growth Factor Receptor Type 2-targeted Contrast-enhanced US of Pancreatic Cancer Neovasculature in a Genetically Engineered Mouse Model: Potential for Earlier Detection. Radiology (2015)

Foygel, K., et al. Detection of pancreatic ductal adenocarcinoma in mice by ultrasound imaging of thymocyte differentiation antigen 1. Gastroenterology (2013)

Pan, S., et al. Multiplex targeted proteomic assay for biomarker detection in plasma: a pancreatic cancer biomarker case study. J Proteome Res.(2012)

Brentnall, TA., et al. Pancreatic cancer surveillance: learning as we go. Am J Gastroenterol. (2011)

Chen, R., et al. Elevated level of anterior gradient-2 in pancreatic juice from patients with pre-malignant pancreatic neoplasia. Mol Cancer (2010)

Chen R, et al. Pilot Study of Blood Biomarker Candidates for Detection of Pancreatic Cancer. Pancreas (2010)

Faca, V., et al. A mouse to human search for plasma proteome changes associated with pancreatic tumor development. PloS Med. (2008)

Chen R., et al. Comparison of pancreas juice proteins from cancer versus pancreatitis using quantitative proteomic analysis. Pancreas (2007)

Chen R., et al. Quantitative proteomics analysis reveals that proteins differentially expressed in chronic pancreatitis are also frequently involved in pancreatic cancer Mol. Cell. Proteomics (2007)

Pogue-Geile, K.L., et al. Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. PloS Med. (2006)

Chen R., et al. Quantitative proteomic profiling of pancreatic cancer juice. Proteomics (2006)