What is pancreatic cancer?

When Steve Jobs died on October 5^th of this year, global attention turned to his cause of death – pancreatic cancer. Many people had questions: Would his fate have been different if he hadn’t elected for alternative treatments in the early days of his diagnosis? If someone of his wealth couldn’t beat this disease, can anyone? What many people may not know is that the eight years Jobs lived with his cancer diagnosis were significantly longer than the typical pancreatic cancer patient can expect to survive. This fact has much, if not all to do with the particular type of pancreatic cancer that Jobs had.

There are two parts of the pancreas: the endocrine pancreas and the exocrine pancreas. The former secretes hormones like insulin that help control blood sugar levels, while the latter secretes digestive enzymes that help break down the food you eat. Steve Jobs fell into the 1% of patients whose pancreatic cancer is of endocrine origin, and these patients have better prognoses because cancers of the endocrine pancreas are less aggressive. The other 99% of pancreatic cancer patients have exocrine tumors, most commonly in a form called an adenocarcinoma, and their prognosis is not so good: these tumors have a five-year survival rate of less than 5% compared to a 50 to 80% survival rate for endocrine tumors [1]. Why is the outlook for adenocarcinomas so poor? It has everything to do with what happens before a patient ever makes a trip to the doctor.

How is pancreatic cancer detected?

You’ve been feeling abdominal pain and throwing up for a few days, but you assume it’s just a nasty stomach virus. However, when you start to notice that the whites of your eyes are looking a bit yellowish, you decide to go in to see your doctor. The diagnosis: you have pancreatic cancer; your primary tumor is already quite large and has more than likely spread to other parts of the body – and you’re one of the luckier ones. The ability to detect pancreatic tumors can depend on which part of the pancreas the tumor originates from. When a pancreatic tumor is near the common bile duct, a buildup of bile in the blood can cause the yellow-tinged skin characteristic of jaundice. The unanticipated benefit of this symptom is that it brings attention to the fact that a tumor may be present. People with pancreatic tumors originating elsewhere on the pancreas can go much longer before having any clue that something is wrong with them.

Because there are few, if any, symptoms in the early stages of pancreatic cancer, few patients are diagnosed early on, when surgery could be more useful because the cancer has not yet spread. Additionally, there are no general screening tools to catch pancreatic cancer early, in contrast to the regular mammograms used to detect breast cancer in women, for example. Even with some sort of early screening, pancreatic cancer can still go undetected by most imaging methods because of its location deep in the abdomen, beneath the liver and behind the stomach; it is known as “the hidden organ.”

Figure 1. The pancreas is effectively “hidden” by other organs, making pancreatic tumors difficult to detect by many imaging methods.

How is pancreatic cancer treated?

A year or two ago, the standard treatment for pancreatic cancer was chemotherapy, a very non-specific way of killing rapidly dividing cells in the body. While the targets of chemotherapy include the fast-growing cancer cells, other tissues like hair and the lining of the gut are also harmed, which makes for unpleasant and potentially serious side effects for the patient. Most of the current and pending treatments for pancreatic cancer are much more focused on the specific biology of pancreatic tumors. Today, patients are often given Tarceva, a drug that inhibits a growth-promoting molecule produced by the tumor. Combined with standard chemotherapy, Tarceva can significantly extend the life of patients [2].

A growing number of pancreatic cancer treatments in clinical trials work by helping our immune system specifically target and destroy cancer cells. These therapies use antibodies – molecules that are naturally produced by the immune system and bind to specific cells, marking them for destruction. The National Cancer Institute is attempting to engineer an antibody that binds pancreatic cancer cells, causing them to be recognized and killed by immune cells [3]. This antibody could be combined with standard chemotherapy to create a more potent effect against the cancer.

Another potential therapy in development for pancreatic cancer is the use of viruses to selectively target and kill cancer cells. The concept behind this therapy is that researchers can modify viruses to recognize molecules found exclusively in cancer cells. When such a virus is administered, it infects cancer cells and causes them to die, leaving normal tissues unharmed and spreading only to tumors. Clinical trials have been done in humans with virus-based therapies in recent years, and the results are promising [4].

Can we detect pancreatic cancer earlier?

Still, the difficulty in detecting pancreatic cancer in its early stages remains at the heart of why this disease is so deadly. One way to address this problem is by using improved imaging techniques, an area that has seen promising breakthroughs in recent years. One such technology involves the use of a simple endoscopy, in which a thin tube with a light at the end is passed into the upper part of the small intestine to see inside the body. This approach is based on the principle that a tumor in one part of the pancreas would alter the structure of the entire organ. Because the head of the pancreas is in contact with the upper intestine, an endoscopy could detect a meaningful change in pancreas structure early on in the cancer. An experiment showed this technique to be effective in identifying 19 out of 20 early-stage pancreatic tumors in patients.

Another cutting-edge imaging method under consideration takes advantage of a biomarker for early-stage pancreatic cancers. A biomarker is any biological substance that can be used to indicate a particular biological state; for example, a protein that is significantly more abundant in the blood of people with pancreatic cancer would be a biomarker for the disease. Identifying biomarkers for early-stage pancreatic cancers is an area of active study because they could make detecting these cancers much easier. Doctors could simply draw a blood sample and have an indication that a patient may have pancreatic cancer, at a time when the tumor is still operable. Fascinatingly, researchers at UCLA showed last year that they could detect biomarkers in saliva that were significantly different between people with pancreatic cancer and people who were only at risk for it [5]. This noninvasive technology could be ideal for screening at-risk groups for pancreatic cancer, including people with chronic pancreatic inflammation and those with recent-onset diabetes.

The last few years have seen large strides in research to understand what sets pancreatic cancer apart, and to change how this disease is diagnosed and treated. These advances all provide hope for a future, perhaps only a few short years away, in which pancreatic cancer is not so silent a killer – or not as much of a killer at all.

Kristin Rose is PhD candidate at Harvard Medical School.

References:

1. “Pancreatic cancer survival by stage,” American Cancer Society, October 20 2010, <http://www.cancer.org/Cancer/PancreaticCancer/DetailedGuide/pancreatic-cancer-survival-rates>
2. Malcolm J. Moore et al, “Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group,” Journal of Clinical Oncology, May 20 2007, Vol 25, pgs 1960-1966
3. Elizabeth Landau, “Why pancreatic cancer is so deadly,” CNN Health, October 6 2011, http://www.cnn.com/2011/10/06/health/conditions/pancreatic-cancer-steve-jobs/index.html
4. Ta-Chiang Lu, “Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress,” Nature Reviews Clinical Oncology, February 2007, Vol  4, pgs 101-117
5. Lei Zhang et al, “Salivary Transcriptomic Biomarkers for Detection of Resectable Pancreatic Cancer,” Gastroenterology, March 2010, Vol 138, pgs 949-957