By William C. Phelps, PhD
Back in May something amazing happened. A 15-year-old high school freshman from Crownsville, MD, Jack Andraka, won the National Intel Science Fair for creating a more sensitive and much less expensive device to detect pancreatic cancer. This is a remarkable achievement for a high school freshman and could be a game-changing discovery for a deadly cancer if it proves successful in future clinical testing, expected to be a number of years away. Only a few months before that, 17-year-old Angela Zhang from Cupertino, CA, won the Siemens Prize for creating laser-activated nanoparticles which kill cancer cells. Clearly, a bright light of innovation is growing in our next generation of young scientists.
Among the hundreds of different cancers that affect people today, perhaps none is more dreadful than pancreatic cancer. Doctors cannot easily detect it, nor are there effective treatments available for the majority of patients. We don't fully understand what causes pancreatic cancer and we know very little about how it can be prevented. The disease is frighteningly aggressive in its growth, with patients often living less than a year after they're diagnosed. Why has progress been so frustratingly slow for pancreatic cancer when compared with other forms of cancer? In general, cancer is considered a very complex collection of diseases, and among cancers, pancreatic cancer is one of the more complicated. It has been an unusually slow process to unravel the biological picture of pancreatic cancer.
The pancreas is a very important gland in the human body that most people know little about. It hides behind the stomach and looks a bit like a flattened sponge maybe 8-10 inches in length. We may have forgotten our high school biology where we learned that the pancreas is part of the digestive system, secreting various enzymes into the intestines to help break down food. In addition, the pancreas manufactures various hormones, including insulin, which helps turn food into the energy needed for life.
Causes and pancreatic cancer prevention
The vast majority of pancreatic cancer occurs randomly in the population. Only a small percentage, perhaps about 5%, seems to run in families. In the past decade, we have learned that obesity, diabetes, tobacco products, and alcohol consumption can increase a person's risk for many types of cancer, including pancreatic.
At a cellular level, research has revealed that damage to a small collection of genes can cause pancreatic cells to become cancerous. Changes or mutations to the KRAS gene are found in about a quarter of all types of cancer but found in more than 90% of pancreatic cancers. Other gene mutations can be found in pancreatic cancer, but none with such high frequency. This suggests that changes in the KRAS gene are one of the primary molecular causes of pancreatic cancer. Research is further showing that a healthy lifestyle can lead to less damage to our genes, including those that can cause pancreatic cells to grow out of control. So the best advice to reduce your risk of pancreatic (and other kinds of) cancer is to eat right and don't smoke!
Finding pancreatic cancer early?
At least today, the short answer is that we can't find it early. Pancreatic cancer usually doesn't cause major or specific symptoms, like a breast lump might signify breast cancer. Because of the critical role of the pancreas in everyday nutrition (manufacturing insulin), it is perhaps surprising that the growth of tumors in the pancreas is often not accompanied by clear symptoms. By the time patients experience symptoms such as abdominal pain, pancreatic tumors are often at an advanced stage where surgery or chemotherapy is very challenging. Under circumstances where it is found early, detection is often accidental.
There are a number of ongoing research studies looking at new imaging techniques to see the early growth of tumors, or tests to detect markers in blood, urine, stool, or saliva. The markers we understand best to date are CEA (carcinoembryonic antigen) and a sugar molecule called CA 19-9. Thus far, though, neither is specific or consistent enough to be useful for early detection. Clearly new markers or methods to detect pancreatic cancer at the earliest possible stage are urgently needed, and there are some promising ones under study now.
Pancreatic cancer treatment and new horizons
Once diagnosed, only a small percentage of pancreatic cancer patients will benefit from surgery to remove the tumor(s). The surgery is considered risky, complicated, and of little benefit if the cancer has spread too far. The majority of patients will receive some combination of chemotherapy and/or radiation therapy. In spite of the many clinical trials of both conventional and more recent, targeted cancer therapies, pancreatic cancer remains one of the most treatment-resistant cancers faced today. Treatment with gemcitabine (Gemzar) with or without targeted drugs such as erlotinib can result in only a few extra months of survival, and it often has uncomfortable side effects that affect quality of life. A quick search of the clinical trials site at the National Institutes of Health lists more than 400 open clinical trials in pancreatic cancer, the majority of which are treatment studies to make current therapies better or test new drug candidates.
One of the recent breakthroughs in understanding why pancreatic cancer is so resistant to treatment has come from the study of the cells and tissue which surround the tumor, the "microenvironment." A somewhat unique characteristic of pancreatic cancer is that the normal cells surrounding the tumor can build a barrier that blocks the body's immune cells, and physically prevents drugs from getting to the cancer cells. One of the promising strategies being actively pursued in the laboratory and in patients focuses on tearing down that wall of tissue to allow chemotherapeutic drugs to better access the tumor. Maybe some of those drugs that failed in the past did so simply because they didn't get to the tumor.
A promising future
The dreadful experience that patients and their families have with pancreatic cancer understandably makes us extremely impatient for advances in prevention, detection, and treatment. We should take heart in the knowledge that a great deal of research currently is being conducted to benefit pancreatic cancer patients in the future. A significant fraction of funding in cancer research is focused on finding answers to fundamental questions for all types of cancers - how cells divide out of control, how tumors escape the immune system, and what allows tumors to metastasize (spread) to sites around the body. The answers from these studies will very likely benefit a very wide range of cancer patients, including those with pancreatic cancer. In addition, genetic studies for one cancer may have great benefits in other cancers. For example, studies of KRAS genes in lung cancer or colon cancer are very likely to benefit those with pancreatic cancer as well (see above, and see my previous blog on this subject). Finally, at their core, research scientists are problem solvers and pancreatic cancer is a terrible problem that many people, scientists included, have had personal experiences with among family and friends. There is no lack of commitment, only a lack of knowledge.
As long as we continue to focus on supporting the best science and the most innovative scientists - people like that very excitable 15 -year -old prodigy from Maryland -- we will succeed in addressing the unmet needs in the many types of cancers we haven't learned how to prevent or treat successfully. Within the last year, Steve Jobs died of a rare form of pancreatic cancer after imagining that we could carry our music and the internet in our pockets. In the future, it will be the imagination of young scientists like Jack and Angela that will change the way we see deadly cancers, and it can't happen too soon.
Dr. Phelps is director of preclinical and translational cancer research for the American Cancer Society.