What’s New in Pancreatic Cancer Research?
Genetics and early detection
Scientists are learning more about some of the gene changes in pancreas cells that cause them to become cancer. Inherited changes in genes such as BRCA2, p16, and the genes responsible for Lynch syndrome 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 are not inherited. Pancreatic cancer actually 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 changes 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 pre-cancerous conditions. One of the most common DNA changes in these conditions affects the KRAS 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.
Other tests are looking to see if groups of proteins found in the blood might be used to find pancreatic cancer early, when it is likely to be easier to treat. Some early results with this approach have been promising, but more research is needed to confirm its usefulness.
A lot of research is focused 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 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 long hospital stay, at least in part because of the long incision (cut) 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 tools 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.
Some studies are looking at different ways to give radiation to treat pancreatic cancer. These include intraoperative radiation therapy (in which a single large dose of radiation is given to the area of the cancer 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).
Many clinical trials are testing new combinations of chemotherapy drugs for pancreatic cancer. Many studies are seeing if combining gemcitabine with other drugs can help people live longer. Other newer chemo drugs are also being tested, as are combinations of chemo drugs with newer types of drugs.
Targeted drugs work differently from standard chemo drugs in that they attack only specific targets on cancer cells (or nearby cells). Targeted therapies 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 is an active area of cancer research.
Growth factor inhibitors: Many types of cancer cells, including pancreatic cancer cells, have certain proteins on their surface that help them grow. These proteins 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): Chemotherapy is not always helpful for pancreatic cancer. This is partly because of the cancer cells themselves. But another reason might be that the dense supportive tissue (stroma) in the tumor seems to form a barrier that helps protect the cancer cells from the chemo drugs. Researchers are now testing drugs such as PEGPH20, which attack the stroma directly to help break it down. This might allow chemo or other drugs to be more effective. This and similar drugs are now in clinical trials.
Drugs that target cancer stem cells: One theory as to why pancreatic cancer is difficult to treat is based on the idea that not all of the cancer cells in a tumor are the same. There might be a small group of cancer cells, called stem cells, that drive tumor growth and are resistant to chemo, so even if the other cells are killed, the cancer will continue to grow. Drugs that are thought to target such stem cells, such as BBI-608 and demcizumab, are now being tested along with chemotherapy, and some early results from these studies have been promising.
Other targeted therapies: Many drugs targeting other aspects of cancer cells are now being studied for use in pancreatic cancer.
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 tend 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. Some of these 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 can predict how well a drug will work before it is given is an important area of research in many types of cancer.
Advances for pancreatic neuroendocrine tumors (NETs)
Many pancreatic NETs have receptors for somatostatin on their cells. This allows these tumors to be detected with imaging tests such as somatostatin receptor scintigraphy (OctreoScan), as well as to be treated with octreotide and other drugs like it.
Newer forms of octreotide have shown even more promise in detecting and treating NETs. For example:
- Gallium-68 (Ga-68) DOTATATE is a slightly radioactive drug that can be used as part of a PET/CT scan to detect NETs. Some research has found that it might be better at this than the OctreoScan.
- Lutetium-177 (Lu-177) DOTATATE is a different radioactive form of this drug that can be used to treat some NETs. It is injected into a vein, and the octreotide portion of the drug brings the radiation directly to the tumor. This type of treatment, known as peptide receptor radionuclide therapy (PRRT), has been shown to shrink some tumors and keep others from growing in early studies.
Last Medical Review: March 14, 2016 Last Revised: May 31, 2016