The Sol Goldman Pancreatic Cancer Research Center

What's New 2011

Johns Hopkins Team Sequences Four Main Cystic Tumors of the Pancreas

Cystic tumors (tumors that forms spaces that contain fluid) of the pancreas can be precancerous. If left in place, some cystic tumors will progress to incurable pancreatic cancer, while others are harmless. These cystic tumors therefore represent on one hand an opportunity to cure pancreatic tumors before they have the opportunity to grow into incurable cancers. On the other hand, since some pancreatic cysts are harmless, these cysts also can be over treated if a harmless cyst is clinically mistaken for a potentially harmful one.

In a real tour de force, the pancreatic cancer research team, led by Dr. Bert Vogelstein, has fundamentally advanced our understanding of the four most common cystic tumors of the pancreas. In findings reported in the December 8th advance on-line edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS), the team announced that they had sequenced all known human genes (>20,000) in 32 cystic tumors of the pancreas: 8 serous cystadenomas (SCA), 8 intraductal papillary mucinous neoplasms (IPMNs), 8 mucinous cystic neoplasms (MCNs), and 8 solid-pseudopapillary neoplasms (SPNs). The team found that each tumor type has its own genetic profile- that is to say that specific genes are targeted in specific tumor types. The VHL gene is targeted in SPNs, the GNAS, RNF43 and KRAS genes in IPMNs, the KRAS, RNF43 and TP53 in MCNs, and the beta-catenin gene in SPNs.

This finding is important for several reasons. First, it provides insight into the fundamental biology of each of these pancreatic tumors. Second, it suggests that the four cysts can be distinguished by their genetic changes. Since the cyst fluid present in these tumors will harbor the same genetic changes as are found in the tumors, this suggests that, in the near future, scientists should be able to diagnose the cyst type just from a small sampling of cyst fluid.


Pancreas Pathology iPad App is Available

iPad in use

We have created a novel tool to teach pancreatic pathology. The Johns Hopkins Atlas of Pancreatic Pathology iPAD application ("app") is a teaching atlas aimed at residents, fellows and practicing pathologists. It contains over 1,400 images and is composed of three modules: an interactive diagnostic algorithm, a searchable image atlas, and an image-based quiz. Viewing multiple examples of the same entity or feature from this large, rich image atlas will strengthen the users diagnostic skills.

The app is available free through the iTunes store. http://itunes.apple.com/us/app/atlas-of-pancreas-pathology/id474845392?mt=8.


New Gene Based Tests Distinguish Harmless & Precancerous Cells

Scientists at the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins reported in the July 20 issue of Science Translational Medicine that they have developed a gene-based test that can be used to distinguish harmless from precancerous pancreatic cysts. The test may eventually help patients with harmless cysts avoid needless surgery.

Fluid-filled cysts are actually fairly common in the pancreas. The problem is that it can be hard to distinguish harmless pancreatic cysts from precancerous cysts.

Bert Vogelstein, M.D., and his colleagues discovered that almost all of the precancerous cysts of the pancreas have mutations in the GNAS and/or the GNAS gene. The researchers then tested a total of 132 precancerous pancreatic cysts for mutations in KRAS and GNAS. Nearly all (127) had mutations in GNAS, KRAS or both. Next, the investigators tested harmless cysts, and the harmless cysts did not have GNAS or KRAS mutations Larger numbers of patients must be studied before the gene-based test can be widely offered. To learn more about pancreatic cysts, visit: http://pathology.jhu.edu/pancreas/cyst/index.php


Scientists at Hopkins Make a Major Advance in the Understanding of Pancreatic Neuroendocrine Tumors

Christopher Heaphy, Roeland De Wilde and Yuchen Jiao in the laboratory of Alan Meeker in the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins reported today (June 30th, 2011) in the on-line edition of the journal Science that they have discovered that pancreatic neuroendocrine tumors have unique chromosome changes called "Alternative Lengthening of Telomeres." Alternative Lengthening of Telomeres affects the ends of chromosomes, the part of the chromosomes called telomeres. The team then showed that Alternative Lengthening of Telomeres in pancreatic neuroendocrine tumors (also known as "islet cell tumors") is likely caused by mutations (DNA changes) in the DAXX and ATRX genes. This finding is important because it uncovers an entirely new cancer pathway. Now that this new pathway has been discovered, the team hopes that this pathway can be exploited diagnostically and therapeutically.


New Book from Johns Hopkins University Press on Pancreatic Cancer

Book CoverDr. Dung T. Le, a medical oncologist at Johns Hopkins, and her patient Michael J. Lippe have teamed together and written a remarkable book on pancreatic cancer. Michael was diagnosed with stage IV pancreatic cancer in 2007, and the book, "Pancreatic Cancer: A Patient and His Doctor Balance Hope and Truth," (Johns Hopkins University Press) chronicles Michael's journal through his diagnosis and treatment. Michael and Dr. Le alternate chapters, providing two perspectives on the disease and on their partnership fighting Michael's illness. Michael and Dr. Le hope that "their honest yet hopeful persoective will help all people with cancer and those who care for them."

View the book here on Amazon.


Exctiting Trial with FOLFIRINOX

The May 12, 2011 New England Journal of Medicine (N Engl J Med 364;19) contains a report by Thierry Conroy, M.D. and colleagues from the Groupe Tumeurs Digestives of Unicancer and the PRODIGE Intergroup in France describing the results of an exciting clinical trial of the drug combination known as "FOLFIRINOX." In this large study 342 patients were randomized to receive FOLFIRINOX or gemcitabine (Gemzar). Six months of chemotherapy were recommended in both groups in patients who had a response, and the primary end point of the study was overall survival. The patients who received FOLFIRINOX did better than the patients who received gemcitibine. The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group, and the median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group. 31% of the patients who received FOLFIRINOX had an objective response versus 9.4% in the gemcitabine group. The treatment is not without its draw backs as the FLORFIRINOX group did have some side effects of therapy, and some of these were serious.

This important studies demonstrates some of the exciting progress that is being made in the treatment of pancreatic cancer.


Islet cell tumors and Endocrine Tumors Sequenced

Investigators in the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins have sequenced all known human genes in a series of ten pancreatic neuroendocrine tumors of the pancreas (also known as islet cell tumors and endocrine tumors). This article appears in the January 20th advance on-line issue of Science magazine called Science Express. This paper is exciting for three reasons:

  1. The investigators found that one-sixth of pancreatic neuroendocrine tumors of the pancreas have mutations in genes coding for proteins in the mTOR pathway. There are drugs currently available (rapalogues such everolimus) that specifically target the mTOR pathway. The findings suggest that doctors should be able select only those patients who will benefit from an mTOR inhibitor (patients whose tumors have a mutation in the mTOR pathway), while sparing patients who would not benefit because their tumors do not have mutations in this pathway.
  2. The investigators discovered a new cancer pathway. They discovered mutations in two genes (ATRX and DAXX) that have not been reported before in any tumor. These are exciting as they provide insight into the fundamental biology of neuroendocrine tumors of the pancreas, and, as scientists learn more about the function of these genes, we hope completely novel therapies.
  3. The scientists found that tumors with both ATRX/DAXX mutations and mutations in another gene (MEN-1) have a significantly better prognosis than do tumors that lack these mutations.

We believe that this sequencing project represents a significant advance in the war against pancreatic neuroendocrine tumors. The results have both immediate and long-term impact.


New Approach to the Early Detection of Cancer

A team of scientists at Johns Hopkins, led by Drs. Bert Vogelstein and Akhilesh Pandey, have developed a new approach to the early detection of cancer, including pancreatic cancer. This advance was published on January 19th in the on-line early edition of the journal Proceedings of the National Academy of Sciences (PNAS, http://www.pnas.org/content/early/recent). Since DNA codes for RNA which in turns codes for proteins, Drs. Pandey and Vogelstein reasoned that they should be able to detect mutations in DNA by carefully studying proteins. Indeed they were. Briefly, using cutting-edge technologies to examine proteins the team was able to show that they can detect very small quantities of mutant proteins. This advance is important because cancer, including pancreatic cancer, is fundamentally caused by DNA mutations (mistakes in the DNA). These mutations (mistakes) can now be detected at the protein level.



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