Research Advances in Pancreas Cancer

At the Kimmel Cancer Center, state-of-the-art is just the starting point of what we provide patients with pancreas cancer. 

Researcher Anirban Maitra created a
system that makes cancer therapies easier
to give to patients.

About 80 percent of patients diagnosed with pancreas cancer will need novel therapies. The goal of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care is to pursue clinical innovation and develop new treatments based on our laboratory discoveries. The transfer of research findings to clinical research has resulted in the development of a pancreas cancer vaccine and other promising therapies.

• Pancreas Cancer Vaccine
   
• Metabolic Pathways for Pancreas Cancer
  Johns Hopkins investigators test and develop drugs that target faulty enzymes that process glutamine, glucose and fatty acids in some pancreatic cancers. Researchers scan patients’ DNA for genes that could benefit from glutamine- and glucose-blocking drugs.

This research was made possible by a $3.75 million grant and clinical trial funding from Stand Up to Cancer, established by the Entertainment Industry Foundation. Funds were raised during a simultaneous, primetime television broadcast on the ABC, CBS and NBC television networks in September 2008.  

Team members on this project include Chi Dang, M.D., Ph.D., vice dean for research at the Johns Hopkins University School of Medicine, Manuel Hidalgo, M.D., Ph.D., director of the Centro Integral Oncológico Clara Campal (CIOCC) in Madrid, Spain, Ralph Hruban, M.D., Kenneth Kinzler, Ph.D., Daniel Laheru, M.D., Anirban Maitra, M.D., Martin Pomper, M.D., Ph.D., Victor Velculescu, M.D., Ph.D., from the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins, and David L. Vander Jagt, Ph.D. of the University of New Mexico.

• The National Familial Pancreas Tumor Registry
  
   
• Pancreas Cancer Genome
  
  The complete genetic blueprint for lethal pancreas cancer and brain cancer was deciphered by a team at the Johns Hopkins Kimmel Cancer Center. The studies, led by the same group who completed maps of the breast cancer and colorectal cancer genomes in 2007, were reported in two articles in the September 5, 2008, issue of Science Express.
  
  Believed to be the most comprehensive result to date for any tumor type, the map evaluated mutations in virtually all known human protein-encoding genes, comprised of more than 20,000 genes, in 24 samples of pancreas cancer and 22 samples of brain cancer. A core set of regulatory gene processes and pathways, about a dozen for each tumor type, were found to be altered in the majority of tumors studied by the researchers. The research is made possible by the Lustgarten Foundation.
  
  

  Decoding the Pancreatic Cancer Genome

  Members of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center decoded the genomes of pancreatic and brain cancer in 2008. Hear more from the laboratory members on their discovery:

  Overview
  
  Potential Implications
  
  Why Pancreatic cancer?
  
  The importance of Pathways

  
  
• Personalized Genome Sequencing
  
  Scientists at Johns Hopkins, including those at the Sol Goldman Pancreatic Cancer Research Center, used personalized genome sequencing on an individual with an hereditary form of pancreas cancer to locate a mutation in a gene called PALB2, responsible for initiating the disease. The discovery marks the first use of a genome scanning system to uncover suspect mutations in normal inherited genes. The scientists believe the findings underscore the value of personalized genome sequencing, which decodes a person's genes and compares the changes to those found in healthy people.
  
  This research is made possible by the support of The Lustgarten Foundation, The Virginia and D.K. Ludwig Fund for Cancer Research and The Sol Goldman Charitable Trust and The Lillian Goldman Charitable Trust.
  
  
• Rapid Autopsy Program
  
  Investigators are using a new approach to understand the root causes of pancreas cancer through a rapid autopsy program. In this selfless endeavor, pancreas cancer patients who have lost their fight against the disease are allowing investigators to study their tumors, cells and genes to make advances against pancreas cancer. More than 80 rapid autopsies have already been done, allowing investigators to look for genetic differences in pancreas cancer. The program already has helped link a gene to pancreas cancer metastasis.

• Mouse Models
  
  Investigator James Eshleman, M.D., Ph.D., has developed a mouse that grows pancreas cancer cells providing some of the groundwork for a massive exploration of the pancreas cancer genome. Ralph Hruban, M.D., and Eshleman are working with Bert Vogelstein, M.D., in the sequencing of 24,000 known genes and then validating them in some 96,000 pancreas cancers.

• Preventing Pancreas Cancer

Endoscopy

Our endoscopy specialists help people with a family history of pancreas cancer learn if they have precancerous lesions that could develop into cancer. Early precancerous lesions can be surgically removed and the pancreas saved. Some patients may choose prophylactic removal of the pancreas to stave off cancer.

Nanopill

Johns Hopkins scientists combined nanoscience with the Indian spice curcumin to develop a novel pancreas cancer prevention strategy. Curcumin has the ability to activate cancer detoxifying enzymes, but is not absorbed well by cells when eaten. To overcome the absorption problem, the investigators created a nanoparticle carrier for the curcumin. The engineered nanocurcumin can be given intravenously or orally.

Recruiting Genes to Kill Cancer

The Johns Hopkins Kimmel Cancer Center team who discovered the pivotal genes abundant in pancreas cancer patients also is investigating the potential for gene therapy. Studies suggest that a tumor suppressor gene, DCP4, is either missing or inactivated in more than half of all patients with pancreas cancer. Losing the function of both copies of this gene is like losing the brakes on a car. When left unchecked, these cells begin to multiply. Studies are under way to see whether bystander genes can be activated to replace the lost tumor suppressor function and put the brakes on cancer cells.

• Pancreas Cancer Stem Cells
  
  Cancer stem cells are small in number, almost undetectable, but they can be the fuel that promotes certain cancers to grow and spread. Recent research has brought these cells into focus. Johns Hopkins scientists have developed a method to identify cells marked with the proteins CD44 and CD24 and those with high levels of the enzyme aldehyde dehydrogenase, believed to be characteristics of pancreas cancer stem cells.
  
  The investigators found that pancreas cancer stem cells marked with aldehyde dehydrogenase indicated decreased survival. Researchers are working to further define pancreas cancer stem cell populations and decipher the processes that control them. Using drugs to target cancer stem cells has provided new therapeutic strategies for other cancers, and these advances could be applied to pancreatic cancer.
  
  
• The Pancreatic Cancer Action Network and the American Association for Cancer Research have awarded Zeshaan A. Rasheed, M.D., Ph.D., of the Johns Hopkins Kimmel Cancer Center, the 2010 Pancreatic Cancer Action Network-AACR Pathway to Leadership Grant. This grant, totaling $600,000 over five years, will support Rasheed’s efforts to examine the relevance of cancer stem cells in pancreatic adenocarcinoma.
  
  Cancer stem cells are a subset of cells hypothesized to mediate the growth and spread of cancer. Rasheed earned his medical degree and doctorate in cellular and molecular pharmacology from the University of Medicine and Dentistry of New Jersey – Robert Wood Johnson Medical School and Graduate School of Biomedical Sciences. Currently, he is a medical oncology fellow at The Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins. . His research focuses on how different populations of pancreatic cancer stem cells are related to one another and which factors regulate cancer stem cell growth and spread throughout the body. By making these determinations, Rasheed will then investigate how cancer stem cell inhibition is possible, which may lead to the development of novel cancer stem cell-targeting therapies. The grant will be formally awarded at the AACR Annual Meeting on April 20, 2010. The term for the grant begins on July 1, 2010.

• Targeting Genes That Make Therapies Work Better
  
  Three genes, BRCA2, FANCC, and FANCG, have long been linked to a rare, inherited disease known as Fanconi’s Anemia (FA) and appear to play a role in 10 percent or more of pancreas cancers. People affected are born with only a single, normal copy of one or more of the genes. Though they do not develop FA, these people often develop pancreas cancer, usually in their 40s and 50s, about a decade earlier than the average person who develops the disease.
  
  Investigators believe these gene mutations may be the tumor's Achilles' heel of the tumor and make these particular cancers more responsive to treatment. The presence of these three genes appear to make pancreas cancer cells highly susceptible to treatment with two FDA-approved cancer drugs, mitomycin C and cisplatin.

• Calculating Cancer Risk
  
  A novel computer software tool, called PancPRO, helps identify people at risk of developing pancreas cancer because they have inherited gene alterations linked to the cancer. The program's calculator computes the likelihood that a person carries a pancreas cancer-related gene and the person’s lifetime risk of developing this disease. Physicians and genetic counselors use the tool to identify people who may benefit from pancreas cancer screening.
  
  
• Misdirected Cell Pathway
  
  
  Johns Hopkins researchers have uncovered a genetic defect that may be triggering the development of pancreas cancer. A growth signal that should be turned off in adult tissues is mistakenly turned back on. The growth signal appears to be activated in response to injury to, or inflammation of  the pancreas. Investigators suspect that reactivation could be a first step in the initiation of pancreas cancer, occurring even before gene alterations.