U-M Comprehensive Cancer Center scientists are studying stem cells in pancreatic cancer, looking for new and more effective treatments for patients with this deadly diseasePancreatic cancer is one of the deadliest types of cancer. It is the fourth most common cause of cancer deaths in the United States. More than 43,000 people are diagnosed with pancreatic cancer each year and about the same number die each year from the disease. Only about 3% of people with pancreatic cancer live more than five years after diagnosis.
There are several reasons why this type of cancer is so lethal
- Pancreatic cancer is agressive
Not only is it much more aggressive than other types of cancer, it's also quicker to metastasize or spread to other parts of the body.
- It usually is not diagnosed until it's in an advanced stage.
- Unlike other types of cancer, pancreatic cancer responds very poorly to current chemotherapy and radiation treatments.
Scientists at the U-M Comprehensive Cancer Center are studying pancreatic cancer in an effort to find new and more effective treatments for patients with this deadly disease. In 2007, Cancer Center scientists were the first to identify a small group of cells, called cancer stem cells, in tumors from patients with pancreatic cancer. Researchers believe these stem cells are the key to finding an effective treatment and possibly someday a cure for pancreatic cancer.
U-M research shows that just a few cancer stem cells are responsible for the growth and spread of pancreatic cancer. Unless these stem cells are destroyed, the cancer will return. The goal of U-M scientists is to develop a new therapy targeted directly at cancer stem cells. If successful, it will be a major step forward in the treatment of pancreatic cancer.
How will this research help patients with pancreatic cancer?
Since pancreatic cancer is resistant to chemotherapy and radiation, new treatments are needed that can kill the small number of cancer stem cells within the tumor. Studying pancreatic cancer stem cells will help researchers identify targets for new drugs or therapies, which can then be tested in animals and eventually in human clinical trials.
Two clinical trials to target pancreatic cancer stem cells are currently underway at the U-M Cancer Center. The first study is evaluating the toxicity and effectiveness of an experimental drug called GDC-0449, which inhibits a stem cell signaling pathway called hedgehog. The drug is being tested in patients with advanced pancreatic cancer who also are receiving a conventional chemotherapy drug. Biopsies will be examined to see if the number and percentage of cancer stem cells in the tumor changes after treatment with GDC-0449.
The second clinical trial is for patients with pancreatic cancer that can be removed surgically. In this study, the rationale is to use a drug targeting cancer stem cells to minimize cancer recurrence after surgery. Eligible patients receive two weeks of a drug, GSI, which inhibits the Notch signaling pathway, followed by an operation to remove the tumor. Patients will then receive standard chemotherapy, either alone or in conjunction with GSI. The effect of GSI on cancer stem cells and clinical outcomes will be assessed.
For more information about clinical trials, please contact our Cancer Answerline™ at 800-865-1125.
How do scientists tell the difference between pancreatic cancer stem cells and other cells in the tumor?
There are many types of cells in a tumor, but cancer stem cells have specific properties that help scientists identify them. Only cancer stem cells can divide to make exact copies of themselves, and also make progenitor cells that go on to form all the cell types in the patient's tumor. Scientists look for specific signaling pathways and cell surface markers found in cancer stem cells. The ultimate test is to inject human cells into a mouse whose immune system has been suppressed. If the mouse develops a tumor that matches the patient's tumor, then this supports these cells as representing cancer stem cells.
Do pancreatic cancer stem cells have a "fingerprint"?All cells have a unique pattern of proteins, like a fingerprint, on their surface membranes. In 2003, scientists at the U-M Comprehensive Cancer Center discovered that breast cancer stem cells have a surface protein marker called CD44. So researchers looked for cells from pancreatic tumors with high levels of CD44 on their outer membranes.
They found that pancreatic cancer stem cells can be identified by the presence of three protein surface markers called CD44, CD24 and ESA. Recent work suggests that c-Met is another important marker on the cell surface of cancer cells. Other cells in pancreatic tumors don't have this combination of protein markers. These surface proteins help pancreatic cancer stem cells stick to other cell surfaces. They also trigger important signaling pathways between stem cells and their environment.
How common are pancreatic cancer stem cells?
U-M researchers found that only 0.5% to 1% of cells from pancreatic tumors contained the unique cancer stem cell fingerprint of three protein surface markers called CD44, CD24 and ESA.
Are pancreatic cancer stem cells the same as those found in other types of cancer?
Pancreatic cancer stem cells have some similarities to cancer stem cells found in other types of cancer; however, there also appear to be some significant differences. This is why it is important to study the function of these cells in the specific cancer in which these cells arise to best understand their function. Regardless of the organ in which they are found, cancer stem cells appear to be responsible for the propagation of cancer and for its spread to other organs in the body. But they may do this in different ways.
While many cancer stem cells may have one or two protein surface markers in common, scientists have not identified a universal fingerprint for all cancer stem cells. Scientists still don't know if all cancer stem cells use the same signaling pathways to drive the development of cancer.