Pancreatic cancer has the #1 fatality rate of all cancers and is the 3rd leading cause of cancer deaths in the U.S. for both men and women. With an increasing mortality rate, no warning signs and no early detection pancreatic cancer will continue to be the “silent killer,” brutally and quickly taking the lives of loved ones. It is estimated that this year nearly 53,070 Americans will be diagnosed with cancer of the pancreas and approximately 41,780 people will die that same year.
Since 2013 The JCM Foundation has been supporting Dr. Laura D. Wood, MD, PhD/Department of Pathology, Johns Hopkins University School of Medicine. Her research team has been studying invasive pancreatic cancer.
Invasive pancreatic cancer is an aggressive deadly cancer with a dismal prognosis. However, invasive pancreatic cancer arises from non-invasive precursor lesions that, if detected early enough, are curable. Some of these precursor lesions are only visible microscopically, while others form large cysts that are detectable using currently available imaging technologies. While the goal is to remove these precancerous cysts before they progress to an invasive cancer, in some cases the resected precancerous cysts harbor a small associated invasive pancreatic cancer – these lesions provide a unique opportunity to understand the process of malignant transformation.
The JCM Foundation is also supporting Dr. Nicholas Roberts Vet.M.B. PhD,/Department of Pathology, Johns Hopkins University School of Medicine. He’s an innovative researcher dedicated to deciphering the genetic and biological basis of pancreatic cancer risk and translating these developments into personalized screening, early detection methods and novel therapies for patients.
His cutting-edge graduate and postdoctoral work was conducted in the laboratory of accomplished cancer researchers, Drs. Bert Vogelstein and Kenneth Kinzler. During this time, Dr. Roberts set out to understand pancreatic cancer risk using next-generation sequencing technologies. In doing so, he discovered a new familial pancreatic cancer susceptibility gene and developed a mathematical model of disease risk in the general population to determine the ability of personal genome sequencing to predict disease. His work has also extended into comparative models of cancer, where his efforts testing a novel cancer therapy have led to a human clinical trial. These pioneering studies were published in the high-profile journals Science Translational Medicine and Cancer Discovery. Dr. Roberts’s work continues to focus on the genetic and biological determinants of familial pancreatic cancer risk.
Since 2013 The JCM Foundation has been supporting the research of Dr. Volkan Adsay, M.D. Emory University. Dr. Adsay’s research has identified new guidelines for Intraductal Papillary Mucinous Neoplasms (IPMN). IPMN’s are more complicated than first thought, according to Dr. Adsay. Experts on IPMN’s have written a new guideline on their pathologic evaluation and reporting, which was published online March 13, 2015 in the Annals of Surgery (Adsay V, et al.2015) “The tumor type is relatively new and not well know,” says Dr. Adsay. ”There’s been a big learning curve for both pathologists and clinicians. And it’s still a challenging tumor type, both for management and diagnostic purpose.”
Since 2002, the Joseph C. Monastra (JCM) Foundation for Pancreatic Cancer Research has been supporting Dr. Chris Iacobuzio-Donahue’s laboratory at Johns Hopkins, who in that time has made great strides towards understanding how pancreatic cancers develop and spread. Dr. Iacobuzio-Donahue held the position of Professor of Pathology & Oncology in the Sol Goldman Pancreatic Cancer Research Center at The Johns Hopkins University School of Medicine.
Some of that critical research supported in part by the JCM Foundation over the past 12 years at Johns Hopkins includes:
One of the most recent groundbreaking research projects funded in part by the Joseph C. Monastra Foundation was the genetic study lead by Dr. Iacobuzio that revealed a large window of opportunity for the early detection of pancreatic cancer published in Nature (2010 Oct 8:467(7319):1114-7). According to Dr. Iacobuzio, pancreatic cancer develops and spreads much more slowly than scientists have thought.
Using whole genome sequencing data generated from the cancer tissues of seven patients who underwent a rapid autopsy, Dr. Iacobuzio and colleagues found that it takes at least a decade after the first cancer-causing mutation occurs in a normal cell in the pancreas until the development of a full-fledge cancer cell. “For the first time, we have a quantifiable estimate of the development of pancreatic cancer, and when it would be best to intervene,” according to Dr. Iacobuzio. “So there is potentially a very broad window for screening.”
Dr. Iacobuzio and colleagues reported the complete DNA sequence of the pancreatic cancer genome in the journal Science (Science 321:1801). The scope of this sequencing project is unparalleled -simply put, we now know more about the genetic sequence of pancreatic cancer than we do of any other cancer type.
In this study, more than 20,000 genes were analyzed for mutations, deletions or expression changes in 24 pancreatic cancers. Incredibly, each pancreatic cancer only contained an average of 63 mutated genes. These mutated genes were found to correspond to twelve different “core” features of pancreatic cancer cells. This is important because abnormal function of these core pathways and processes can explain the major features of pancreatic cancer formation, and may form the basis for new ways to diagnose and treat pancreatic cancer.
Dr. Iacobuzio-Donahue’s lab has made the striking discovery that there is not one type of pancreatic cancer, but instead there are at least two types of pancreatic cancer. While these two types of pancreatic cancer appear similar at diagnosis, they differ dramatically in that one type continues to grow within the pancreas and destroys surrounding organs and tissues, whereas the second type quickly spreads (“metastasizes”) to other organs.
Mutations in a single gene called DPC4 (deleted in pancreatic cancer 4, one of the 63 mutated genes identified in the genome sequencing effort) were commonly found only in the metastasizing form of pancreatic cancer. This is a huge step forward as it suggests that one of the reasons for the failure of many clinical trials is that we have been unknowingly comparing these two types of cancer, in essence comparing “apples” to “oranges”. This finding was reported in the March 2009 issue of the Journal of Clinical Oncology.
In January 2012 John Hopkins officially announced that in December 2010 Dr. Iacobuzio-Donahue was promoted to Full Professor of Pathology, Oncology and Surgery, a milestone she reached 8 years sooner than the average age of all newly appointed full professors at Johns Hopkins. This comes at a time when she also is embarking on a new research effort (in part supported by the JCM Foundation) to define the clonal evolution of metastatic disease as a follow-up on her findings published in Nature in 2010.
She is also an affiliate faculty member of the Center for Epigenetic Studies. We are also proud to report that Dr. Iacobuzio-Donahue’s success has been acknowledged at the national level. At the annual meeting of the United States and Canadian Academy of Pathology in Boston, she was awarded the Ramzi Cotran Young Investigator Award. This award recognizes an individual under the age of 45 years who has made a significant life-time contributions to the understanding of human disease.
Now that the DNA sequence of the pancreatic cancer genome has been solved, an important next step has been to determine how this information can be used to benefit patients. In the most recent study to date published by Dr. Iacobuzio-Donahue and colleagues, they found that there are reproducible patterns in which the four most commonly mutated genes in pancreatic cancer are mutated in the same pancreatic cancer, a concept of tremendous significance for screening efforts based on identification of these four mutated genes in blood. They also showed that the total number of mutated genes itself is independently correlated with
patient outcome. For example, patients with three or four mutated genes were significantly more likely to develop metastases, whereas patients with only one or two of these genes mutated in their carcinoma had a relatively longer survival, a finding of significance for early identification of long-term survivors. This study was published in the journal Clinical Cancer Research.
For more information on these research efforts supported in part by the Joseph C. Monastra Foundation and Dr. Iacobuzio-Donahue please visit our website: www.jcmfoundation.org