Improving understanding of the mechanism and timing of pancreatic cancer metastasis

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Improving understanding of the mechanism and timing of pancreatic cancer metastasis

The January 20, 2012 edition of the very prestigious journal Cell included two research articles and an overview related to pancreatic cancer metastasis (spread). The overview describing the two articles was coauthored by Dave Tuveson, MD, PhD, recipient of a 2003 Pancreatic Cancer Action Network Career Development Award and current Chair of our Scientific Advisory Board.

The first article describes research that primarily took place in the laboratory of Ben Stanger, MD, PhD at the University of Pennsylvania. Dr. Stanger received a Pancreatic Cancer Action Network Career Development Award in honor of Ralph Hruban, MD in 2007, and our funding is cited as partially supporting the project described in this research article. Additionally, Jennifer Bailey, PhD contributed to the study, and her 2011 Pancreatic Cancer Action Network Pathway to Leadership grant is also mentioned among the sources of funding. Other authors include Anirban Maitra, MD (2004 Pancreatic Cancer Action Network Career Development Award and member, Scientific Advisory Board) as well as Scientific Advisory Board members Anil Rustgi, MD and Bob Vonderheide, MD, DPhil.

Dr. Stanger and colleagues utilized a mouse model previously developed by Dr. Tuveson while he was funded by his Pancreatic Cancer Action Network grant, whereby mice are genetically programmed to develop pancreatic cancer. Dr. Stanger was able to move a step further by marking the cells that carry the mutations necessary to become cancer cells with a yellow fluorescent light so he could visibly follow them through the stages of cancer progression.

The development of pancreatic cancer in these mice has been shown to mimic the progression of human disease. In both humans and mice, the earliest evidence of abnormalities is in the form of precancerous lesions called PanINs. PanINs can develop into pancreatic cancer, and the cancer cells can eventually depart the tumor, enter the bloodstream, and then leave the bloodstream to form metastatic tumors elsewhere in the body. Surprisingly and contrary to previous thinking, Dr. Stanger and colleagues show that mutated pancreatic cells can be found in the bloodstream even when only PanINs are detectable in the pancreas. Importantly, this process is enhanced in the presence of inflammation, consistent with observations that chronic pancreatitis is a risk factor for pancreatic cancer. From a clinical standpoint, these disseminated cells may be detectable early in the disease progression and could therefore aid in the detection and diagnosis of pancreatic cancer.

Whereas Dr. Stanger’s work focused on the earliest stages of pancreatic cell dissemination outside of the tumor, the second article in this edition of Cell looked at end stages of metastatic disease. This paper was based on work primarily out of the laboratories of Christine Iacobuzio-Donahue, MD, PhD at Johns Hopkins University and Franziska Michor, PhD at Harvard. Dr. Iacobuzio-Donahue received a 2007 Pancreatic Cancer Action Network Pilot Grant, and is currently a member of our Scientific Advisory Board. Joe Herman, MD, recipient of a 2008 Pancreatic Cancer Action Network Career Development Award generously funded by the Blum-Kovler Foundation, was also an author on this study.

Dr. Iacobuzio-Donahue and her colleagues conducted their experiments on samples from patients who courageously volunteered for the rapid autopsy program at Johns Hopkins. This program allows evaluation of the patients’ disease immediately after their death, so that the primary tumor and metastatic disease can be directly measured and studied. Moreover, the autopsy findings could be compared to each patient’s pancreatic tumor and metastases as detected at diagnosis. Combining these results, and accounting for any treatment(s) the patient received, Dr. Iacobuzio-Donahue was able to demonstrate the rapidness of metastatic growth, presence of micro-metastases even when disease is thought to be confined to the pancreas, and therefore the importance of systemic (whole-body) treatment in the fight against pancreatic cancer at all stages.

Together, these two important articles shed light on the process and timing by which pancreatic cancer cells are able to leave the pancreas, survive in the bloodstream, and colonize in other organs. Although the results reinforce the aggressive nature of pancreatic cancer, a better understanding of the disease progression can pave the way for development of improved diagnostic and treatment options. These articles also illustrate that our research grant program is helping to create a vibrant pancreatic cancer community. We are extremely proud that scientists that we have funded are continuing their work in pancreatic cancer and going on to make valuable contributions to the field.

For more information about these studies or other questions about pancreatic cancer disease progression, diagnosis, or treatment, please contact a Pancreatic Cancer Action Network Patient and Liaison Services (PALS) Associate toll-free at 877-272-6226 or email PALS Associates are available M-F 7am-5pm Pacific Time.

Click here and here to read Dr. Stanger and Dr. Iacobuzio-Donahue’s scientific abstracts, respectively.
Click here to see the University of Pennsylvania press release describing Dr. Stanger’s work, with a quote from Pancreatic Cancer Action Network Vice President of Scientific and Medical Affairs, Lynn Matrisian, PhD.

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