What’s new in pancreatic cancer research and treatment?

Research into the causes, diagnosis, and treatment of pancreatic cancer is under way in many medical centers throughout the world.

Genetics and early detection

Scientists are learning more about some of the changes in DNA that cause cells in the pancreas to become cancerous. Inherited changes in genes such as BRCA2, p16, and the genes responsible for hereditary non-polyposis colorectal cancer (HNPCC) can increase a person’s risk of developing pancreatic cancer.

Researchers are now looking at how these and other genes may be altered in pancreatic cancers that do not seem to be inherited. They have discovered that pancreatic cancer does not form suddenly. It develops over many years in a series of steps known as pancreatic intraepithelial neoplasia or PanIN. In the early steps, such as PanIN 1, there are changes in a small number of genes, and the duct cells of the pancreas do not look very abnormal. In later steps such as PanIN 2 and PanIN 3, there are abnormalities in several genes and the duct cells look more abnormal.

Researchers are using this information to develop tests for detecting acquired (not inherited) gene changes in pancreatic cancer pre-cancerous conditions. One of the most common DNA changes in these conditions affects theKRAS oncogene, which affects regulation of cell growth. New diagnostic tests are often able to recognize this change in samples of pancreatic juice collected during an ERCP (endoscopic retrograde cholangiopancreatography).

For now, imaging tests like endoscopic ultrasound (EUS), ERCP, and genetic tests for changes in certain genes (such as KRAS) are options for people with a strong family history of pancreatic cancer. But these tests are not recommended for widespread testing of people at average risk who do not have any symptoms.

Treatment

The major focus of much research is on finding better treatments for pancreatic cancer. Improving surgery and radiation therapy are major goals, as is determining the best combination of treatments for people with certain stages of cancer.

Surgery

Surgery to remove pancreatic cancer (most often a Whipple procedure) is a long and complex operation that can be hard both for the surgeon and the patient. It often requires a hospital stay of a week or more, at least in part because of the long incision made in the belly.

A newer approach now used at some major medical centers is to do the operation laparoscopically. For this approach, the surgeon makes several small incisions in the belly instead of one large one. Long, thin surgical instruments and a tiny video camera are then inserted through these cuts to do the operation. One advantage of this surgery is that people often recover from it more quickly. But this is still a difficult operation. Surgeons are looking to see how it compares to the standard operation and which patients might be helped the most by it.

Radiation therapy

Some current studies are looking at different ways to give radiation to treat exocrine pancreas cancer. These include intraoperative radiation therapy (in which a single large dose of radiation is given to the pancreas in the operating room at the time of surgery) and proton beam radiation (which uses a special type of radiation that might do less damage to nearby normal cells).

Chemotherapy

Many clinical trials are testing new combinations of chemotherapy drugs for pancreatic cancer. Studies have looked to see if combining gemcitabine with other drugs would help patients live longer. For example, adding capecitabine (Xeloda) to gemcitabine seems to help some patients. The combination of gemcitabine, irinotecan, and celecoxib (an arthritis drug) also shows promise.

Other studies are testing the best ways to combine chemotherapy with radiation therapy or newer targeted therapies.

Targeted therapies

As researchers have learned more about what makes pancreatic cancer cells different from normal cells, they have developed newer drugs that should be able exploit these differences by attacking only specific targets. These targeted therapies may provide another option for treating pancreatic cancer. They may prove to be useful along with, or instead of, current treatments. In general, they seem to have fewer side effects than traditional chemo drugs. Looking for new targets to attack on cancers is an active area of research.

Growth factor inhibitors: Many types of cancer cells, including pancreatic cancer cells, have certain molecules on their surface that help them grow. These molecules are called growth factor receptors. One example is epidermal growth factor receptor (EGFR). Several drugs that target EGFR are now being studied. One, known as erlotinib (Tarceva), is already approved for use along with gemcitabine.

Anti-angiogenesis factors: All cancers depend on new blood vessels to nourish their growth. To block the growth of these vessels and thereby starve the tumor, scientists have developed anti-angiogenesis drugs. These are being studied in clinical trials for patients with pancreatic cancer.

Drugs that target the tumor stroma (supporting tissue): Pancreatic cancer does not always respond well to chemotherapy. This is partly because of the cancer cells themselves, but another reason might be the dense surrounding supportive tissue (stroma) in the tumor. The stroma seems to form a barrier that helps protect the cancer cells from the effects of chemo drugs. Researchers are now looking at drugs that attack the stroma directly to help break it down. This might allow chemo or other drugs to be more effective. Some of these types of drugs are now inclinical trials.

Other targeted therapies: Many drugs targeting other aspects of cancer cells are now being studied for use in pancreatic cancer. Some of these drugs, such as sunitinib (Sutent), have several different targets.

Immune therapy

Immune therapies attempt to boost a person’s immune system or give them ready-made components of an immune system to attack cancer cells. Some studies of these treatments have shown promising results.

Monoclonal antibodies: One form of immune therapy uses injections of man-made monoclonal antibodies. These immune system proteins are made to home in on a specific molecule, such as carcinoembryonic antigen (CEA), which is sometimes found on the surface of pancreatic cancer cells. Toxins or radioactive atoms can be attached to these antibodies, which bring them directly to the tumor cells. The hope is that they will affect cancer cells while leaving normal cells alone. For use in pancreatic cancer, these types of treatments are available only in clinical trials at this time.

Cancer vaccines: Several types of vaccines for boosting the body’s immune response to pancreatic cancer cells are being tested in clinical trials. Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, pancreatic cancer. One possible advantage of these types of treatments is that they seem to have very limited side effects. At this time, vaccines are available only in clinical trials.

Drugs that target immune system checkpoints: The immune system normally keeps itself from attacking other normal cells in the body by using “checkpoints” – molecules on immune cells that need to be activated (or inactivated) to start an immune response. Cancer cells sometimes find ways to use these checkpoints to avoid being attacked by the immune system. Newer drugs that target these checkpoints have shown a lot of promise in treating some types of cancer, and are now being studied for use in pancreatic cancer.

Individualization of therapy

Some drugs seem to work better if certain types of mutations can be found in the patient’s tumor. For example, erlotinib may work better in patients whose tumors have a particular change in the EGFR gene. This concept is an area of intense study. There might also be some gene alterations that affect how well gemcitabine will work in a particular patient. Identifying markers that may predict how well a drug will work before it is given is an important area of research in many types of cancer.

New treatments for pancreatic neuroendocrine tumors (NETs)

Many pancreatic NETs have receptors for somatostatin on their cells. These tumors can be treated with octreotide and other drugs like it. Newer drugs that use a radioactive form of octreotide have been shown to shrink some tumors and keep others from growing in early studies.

Last Medical Review: 06/11/2014
Last Revised: 01/09/2015