Pancreatic (Pancreas) Cancer

• Pancreatic cancer affects the pancreas, an organ found in the abdomen. The pancreas is responsible for producing enzymes that aid in digesting food and hormones like insulin and glucagon that help to balance blood-sugar levels.
  
  
• Pancreatic cancer is relatively uncommon, but almost uniformly fatal. The disease's symptoms, which are often difficult to identify, make if difficult to detect until it is at an advanced stage. It ranks as the fourth-leading cause of cancer-related death in U.S. men and women.
  

• Different types of tumors can occur in the pancreas. The most common type is pancreatic ductal adenocarcinoma, a cancer that is almost always deadly and forms in the cells that help deliver enzymes for food digestion, known as exocrine tumors. Less deadly and far less common are tumors that form in the cells that make the hormones, called endocrine tumors.

Identifying risk factors – The Center is home to the world’s largest population-based study examining environmental and genetic risk factors that contribute to the development of pancreatic cancer. The PACIFIC (Pancreatic Cancer Investigation: Finding Causes) study findings could advance screening and prevention efforts. Learn more »

Developing a groundbreaking research tool – Dr. Sunil Hingorani pioneered one of the most significant breakthroughs in pancreatic cancer research in decades. He helped develop a genetically engineered mouse model that exactly mimics human pancreatic cancer from its precancerous inception to its advanced stages. The model, which is now widely used in research around the world, has opened the door to the discovery of new treatments as well as diagnostic tests for early detection of pancreatic cancer. Learn more »

Early detection – Our researchers are committed to finding news ways to detect pancreatic cancer as early as possible when it is most treatable. Our work includes:

• Dr. Samir Hanash and colleagues have identified a set of proteins associated with the early-stage development of pancreatic tumors in genetically engineered mice. The same five-protein set is also associated with the early development of the disease in humans. The major breakthrough brings scientists significantly closer to developing a blood test to detect pancreatic cancer early, when cure rates are highest. Learn more »
  
  
• An international research group that includes Dr. Teri Brentnall has discovered that the mutated form of a gene called palladin causes hereditary pancreatic cancer. The findings may help define a target for screening and early diagnosis for this often-lethal cancer. Learn more »
  
  
• Another team of researchers led by Dr. Brentnall is developing a blood test that targets pancreatic cancer at its very earliest–and most difficult to detect–stage known as pancreatic carcinoma in situ. The Brentnall team includes collaborators from along the West Coast and Canada and receives support from the Canary Foundation's cancer early-detection program. Learn more »
  
  
• Dr. Paul Lampe and colleagues are using antibody microarrays to search for blood-based proteins that could detect pancreatic cancer at an early stage, when it is most treatable. There is hope that the method may even help identify what subtype of pancreatic cancer a patient has. Lampe is using this same method of searching for blood-based biomarkers for the early detection of breast and ovarian cancers. Learn more »

Understanding pancreatic cancer's progression – Dr. Sunil Hingorani and colleagues have discovered that a specific sequence of otherwise common genetic mutations—not just their mere presence—is responsible for the development of the most common and almost uniformly deadly form of pancreatic cancer: ductal adenocarcinoma. Previously, scientists did not know why cells developed into ductal adenocarcinoma or a less aggressive form of the cancer known as cystic ductal pancreatic cancer. The discovery was made using the first genetically engineered animal model of pancreatic cancer. Learn more »

Treatment resistance – Using the genetically engineered mouse model he developed, Dr. Sunil Hingorani and colleagues have identified several important reasons why pancreatic cancer is resistant to conventional forms of treatment. These discoveries include:

• Reduced blood supply - In 2009, Dr. Hingorani was part of an international research team that uncovered certain characteristics of pancreas tumors that contribute to their drug resistance — and hit on an entirely new strategy for targeting the disease. The team found that not only is pancreas tumor tissue extremely dense — each individual cancer cell is surrounded by a thick conglomeration of fibrous proteins — it also possesses an unusually sparse network of blood vessels. Together, these features insulate pancreas cancer cells, preventing the chemotherapy from penetrating and spreading within the tumor.
  
  Dr. Hingorani and his colleagues used their innovative laboratory model of human pancreas cancer to show that by blocking production of the cancer cells’ dense surrounding tissue, they could increase blood flow to the tumor and significantly improve the chemotherapy’s ability to infiltrate and destroy the cancer. Learn more »
  
  
• Vascular collapse – Pancreas tumors use a unique, two-pronged defense to resist chemotherapy treatment: a greatly reduced blood supply and the creation of an intense and fibrous inflammatory response. The latter includes the production of fibroblasts, immune cells and endothelial cells which become embedded within a dense and complex matrix of proteins and sugar molecules throughout the tumor. Dr. Hingorani’s team discovered that the fibroinflammatory response creates unusually high interstitial fluid pressures which collapse the tumor’s blood vessels and prevent chemotherapies from getting to the tumor. Learn more »

Overcoming resistance – Armed with the knowledge of how pancreatic cancer develops and why it resists treatment, Dr. Hingorani and colleagues are now beginning to research tailored approaches for overcoming the disease’s unique biology. These approaches include:

• New Treatment Strategies – Hingorani’s team recently found that administering an enzyme/chemotherapy combination results in rapid reduction of the interstitial fluid pressure which in turn opens up the blood vessels and permits chemotherapy to reach the tumor. The result was a 70 percent increase in survival time of the mice after the start of treatment.  Learn more »
  
  
• Immunotherapy – Together with other Center scientists, Dr. Hingorani and Dr. Phil Greenberg, a pioneer in T cell immunotherapy, are now examining ways to stimulate the body’s own immune system to fight pancreatic cancer. This may include preventing or reversing the tumor’s ability to tell the immune system not to attack it. This work builds upon the Center’s pre-eminent role in the fields of tumor immunology and immunotherapy.