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Pancreatic Cancer Program

Motivation

Pancreatic cancer is typically detected at late stages when cure is unlikely. Tests to detect pancreatic cancer early are urgently needed in order to save thousands of lives each year.

Pancreatic cancer is a "top ten" cancer killer, causing over 259,000 deaths per year worldwide.1 In the United States, it is the fifth leading cause of cancer-related mortality.2 In 2008, about 37,000 Americans will be diagnosed with pancreatic cancer, and more than 34,000 will die from it.2 The pancreas is located deep inside the body (shaded yellow, left)3 between the stomach and spine and inside a loop of the small intestine. Therefore, small tumors are rarely seen or felt during routine exams. Symptoms of pancreatic cancer often do not appear until the tumor grows large enough or spreads to interfere with the function of nearby organs such as the stomach, small intestine, liver, or gallbladder.

Currently, a diagnosis of pancreatic cancer carries the worst prognosis among all cancers, in part because there are no effective early detection tests and patients are often asymptomatic until advanced stages. The vast majority of cases of pancreatic cancer are diagnosed when cancer has spread to adjacent tissues (Regional Stage) or widely beyond the site of origin (Distant Stage; see Figure 1).4 Consequently, the likelihood of a cure through surgical removal (resection) 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 (Figure 2).4

Figure 1: Stage of Diagnosis Figure 2: Survival by Stage of Diagnosis

In the U.S., the lifetime risk for developing pancreatic cancer is 1 in 79.4 Only about 10% of pancreatic cancer cases are linked to a family history of the disease.5 Thus a major reduction in mortality due to pancreatic cancer will require screening of the general population. Canary Foundation is investing in the development of accurate, reliable and cost-effective tests for the early detection of pancreatic cancer to save lives.

Research

Canary researchers apply a collaborative approach to biomarker discovery, validation, and translation into diagnostic tests for early detection of pancreatic cancer.

Canary is focused on developing diagnostics with high sensitivity and specificity to detect otherwise lethal pancreatic cancers at an early stage when they can be cured through surgical resection. We anticipate that no single biomarker will be sufficient to create a test with the required sensitivity and specificity to detect pancreatic cancer early. Instead, a definitive diagnosis will rely upon combinations of biomarkers and upon blood and imaging tests used together. To this end, the Canary pancreatic cancer team is collaborating to discover and validate biomarkers that will provide the basis for blood and imaging tests for the early detection of pancreatic cancer. We plan to follow up our research by rapidly propelling effective early detection tests into the hands of clinical providers so that patients can begin to benefit as soon as possible.

Blood-Based Biomarkers

Discovery
Our multi-disciplinary approach to biomarker discovery includes cutting-edge gene expression microarray and proteomics technologies and has already led to the identification of a number of candidate biomarkers for pancreatic cancer.

  • We are using proteomics approaches to characterize the proteins found in very early stage pancreatic tumors as a means to discover candidate biomarkers for early stage pancreatic cancer. We have recently expanded the range of samples that we can analyze with such methods by achieving an important technical advance that allows us to recover proteins from pancreatic tumor specimens that were prepared for clinical use.

  • Considering that the development of assays for novel targets is such a cost- and time-intensive endeavor, we continuously invest in optimally prioritizing candidate biomarkers. We are using global gene expression profiles from pancreatic tumors and pancreatic cell lines to prioritize and augment our candidate list. Candidate biomarkers are also evaluated against "baseline" data such as the plasma proteomic data and the normal blood and tissue studies underway as part of Canary's Baseline Program. Ultimately, we are seeking biomarkers that are consistently present at higher (or lower) levels in the blood of individuals harboring early stage pancreatic cancer relative to disease-free individuals.

  • We continue to conduct research to discover key genes that predispose families to inherited pancreatic cancer. Using this approach, we have already uncovered a gene called palladin that is mutated in a certain family with a strong history of pancreatic cancer. We will apply findings from these studies toward discovery of biomarkers for early pancreatic cancer in both inherited and sporadic cases.

Validation
We are implementing a multi-phase approach for biomarker validation that includes testing biomarkers with commercial assays when available, defining core serum sets for testing, and building clinical specimen resources that are crucial to our validation efforts.

  • We are testing a number of candidate biomarkers using commercially-available assays. Biomarkers that perform well using small sets of clinical samples are passed into further rounds of testing on progressively larger numbers of serum samples from pancreatic cases, pancreatitis cases and healthy controls.

  • When commercial assays are not available, the development of assays to measure protein biomarkers is a major bottleneck in accelerating biomarkers through the pipeline to a blood test. Canary has addressed this bottleneck by funding a dedicated team team in Victoria, British Columbia to rapidly develop serum-based assays and validate candidate biomarkers. Our common goal of early detection of pancreatic cancer has allowed Canary Foundation to form a partnership with The Lustgarten Foundation for Pancreatic Cancer Research. Canary Foundation and The Lustgarten Foundation are jointly supporting assay development for pancreatic cancer biomarker candidates at our Victoria facility as part of the Pancreatic Cancer Biomarker Development Project. In conjunction with these efforts, we are utilizing and developing new proteomics-based techniques to qualify our candidate biomarkers.

  • The Canary Pancreatic team is continuously building our specimen resources and is collaborating with multiple institutions to augment our collection with precious pre-diagnostic pancreatic cancer samples and appropriate matched control specimens.

Imaging Biomarkers
Molecular imaging allows us to "see" tumors based on specific, unique, molecular characteristics. We are pursuing a molecular ultrasound approach for early detection of pancreatic cancer. We have engineered microbubbles to bind to specific biomarkers found in the blood vessels that feed tumors and are using ultrasound to image the labeled vessels. Ultrasound is a promising screening tool for early cancer detection because it is highly sensitive, non-invasive, does not use ionizing irradiation, and is routinely available in most imaging departments. We have begun pilot testing of these targeted microbubbles in mice. The long-term goal of this work is to translate molecular ultrasound into a highly sensitive clinical imaging modality for detection of early-stage pancreatic cancer using targeted microbubbles in patients.

View Canary Funded Projects
2008 Pancreatic Cancer Program Progress Report

Citations

  1. Garcia M, Jemal A, Ward EM, Center MM, Hao Y, Siegel RL, Thun MJ. 2007. Global Cancer Facts & Figures 2007. Atlanta, GA: American Cancer Society.
  2. Cancer Facts & Figures 2008. American Cancer Society, Atlanta, GA, 2008.
  3. Image adapted from the image library of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH).
  4. SSurveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 9 Regs Limited-Use, Nov 2008 Sub (1973-2006) - Linked To County Attributes - Total U.S., 1969-2006 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2009, based on the November 2008 submission.
  5. Lynch HT, Smyrk T, Kern SE, Hruban RH, Lightdale CJ, Lemon SJ, Lynch JF, Fusaro LR, Fusaro RM, Ghadirian P. 1996. Familial pancreatic cancer: a review. Semin. Oncol. 23: 251-75.