Current Pancreatic Cancer Research Studies

About 80 percent of pancreatic cancer cases are diagnosed at difficult-to-treat stages when cancer has already spread to nearby tissues or to other organs. That’s why research into new methods to detect pancreatic cancer early could make a huge difference for a lot of people. Research on pancreatic cancer is also focused on developing more effective treatments. New treatments for pancreatic cancer are being developed that could be used alongside surgery to prevent cancer recurrence and for patients with advanced pancreatic cancer, for whom surgery is not an option. Treatment options not yet on the market are available to patients enrolled in pancreatic cancer clinical trials.

Diabetes and early detection of pancreatic cancer

Patients who have their pancreatic cancer detected at earlier stages of disease progression have a better prognosis. None of the current screening tests can catch pancreatic cancer at the stages before symptoms develop. Researchers are looking for better ways to screen for pancreatic cancer so that more people can have a better prognosis at the time of diagnosis, and that’s where diabetes comes in.

Pancreatic cancer can cause diabetes when cancer impairs the ability of cells in the pancreas to secrete sufficient insulin. But the cause and effect can go the other way as well. Living with diabetes for a long time is also a risk factor for developing pancreatic cancer. By mechanisms that are not quite clear, high levels of insulin circulating in the blood, high blood sugar, and long-term inflammation caused by type 2 diabetes seem to contribute to elevated pancreatic cancer risk.

About 1 in 4 people diagnosed with pancreatic cancer were previously diagnosed with diabetes. However, since diabetes is far more common than pancreatic cancer, it isn’t practical to send every person diagnosed with diabetes for pancreatic cancer imaging tests. Fewer than 1 in 100 cases of new-onset diabetes are caused by pancreatic cancer. The New Onset Diabetes (NOD) Study, funded by the National Cancer Institute (NCI) and the National Institute of Diabetes and Digestive and Kidney Diseases, believes they can find a way to sift out those people with early-stage pancreatic cancer from those diagnosed with new-onset diabetes. The NOD study, led by researchers at MD Anderson, aims to develop a blood test that can identify which individuals may need further testing.

The NOD study is enrolling 10,000 participants and will run through 2025. Participants will donate blood periodically for up to 3 years. Researchers will look at biomarkers in the participants’ blood samples. Biomarkers are changes in the types or amounts of biological molecules like proteins. About 85 of the 10,000 participants are predicted to develop pancreatic cancer during the study. Researchers hope to find the specific biomarkers in the blood that are different in those people who later develop pancreatic cancer. In the future, those biomarkers could be used to screen people diagnosed with diabetes to help identify people who might have early-stage pancreatic cancer.

Pancreatic cancer treatments

Standard treatments for pancreatic cancer are surgery, chemotherapy, and radiation therapy. Out of these, surgery has the best outcome, but unfortunately, only 20 percent of pancreatic cancer tumors can be removed by surgery. This motivates researchers to find more effective pancreatic cancer treatments. Some potential treatments are in the pre-clinical stages of research, meaning they have not yet been tested in people. Many pancreatic cancer treatments are being evaluated in clinical trials. The National Comprehensive Cancer Network (NCCN) guidelines recommend clinical trials for certain pancreatic cancer patients at specific stages in their treatment. Certain experts recommend that all pancreatic cancer patients join a clinical trial, even those with early-stage disease. Clinical trials developing new treatments to improve patient care are funded and overseen by the National Cancer Institute (NCI).

Pancreatic cancer clinical trials

After pancreatic cancer surgery, cancer may return if cancer cells are left behind.

Adjuvant chemotherapy

Chemotherapy given after surgery to help eliminate the remaining cancer cells aims to make cancer recurrence less likely. New combinations of adjuvant chemotherapies are being tested in clinical trials to find out if they are better at killing cancer cells after surgery than standard treatments.

Neoadjuvant chemotherapy

Or pre-surgical chemotherapy is given before surgery to shrink the tumor and make it easier to remove. This treatment may also help kill cancer cells that have metastasized from the tumor and prevent cancer from recurring after surgery.

Clinical trials for advanced pancreatic cancer

Patients with advanced or metastatic pancreatic cancer are not able to have their pancreatic tumor removed by surgery because the cancer has spread to other parts of the body. Treatments are being tested in clinical trials that could benefit patients with advanced pancreatic cancer. One strategy is to target cell signals within the tumor cells that make cells grow in an uncontrolled manner. Immunotherapies help the patient’s immune system fight the tumor. Stroma-modifying drugs break down dense tissue that surrounds tumors to help chemotherapy drugs more easily reach cancer cells.

RAS-directed therapies

RAS-directed therapies target the protein RAS in cancer cells. RAS genes code for the production of RAS proteins which act as signals that control cell growth. More than 90 percent of pancreatic cancers have mutations in RAS genes which produce abnormally active RAS protein. Drugs are becoming available that target the abnormal RAS proteins, such as the one caused by the mutation G12C. Although the G12C mutation is not common in pancreatic cancer, researchers are hopeful that this strategy could be used to develop RAS-targeting drugs for mutations that are more common in pancreatic cancer.

Targeting RAS proteins alone doesn’t always work, because cancer cells may find another way to grow and survive. Autophagy is a process that involves reusing and recycling of components inside the cell that cancer cells use to sustain their growth. Researchers are working on a potential one-two punch therapy that targets both RAS signaling and the cellular process autophagy that cancer cells with mutated RAS use to their advantage. The NCI-funded RAS Initiative is working on new therapies for RAS-related cancers.

Immunotherapy

Immune checkpoint inhibitors are a type of immunotherapy that blocks immune checkpoints. Immune checkpoints are an “off signal” that blocks the immune system from responding too strongly and destroying healthy cells in the body. Researchers developed therapies called immune checkpoint inhibitors that prevent the “off” signal from being sent so that immune cells can stay “on” and be more effective at killing cancer cells. Combination immunotherapies that target immune checkpoint inhibitors and enhance the activity of CD40, a protein that activates T cells have been shown to benefit patients with advanced pancreatic cancer. Another immunotherapy approach works to enhance the ability of the white blood cell type called natural killer (NK) cells to kill tumor cells. Immunotherapy therapy drugs are being tested on their own or in combination with other cancer treatments in clinical trials.

Drugs that target the stroma

Stroma is the dense tissue surrounding a tumor that has supportive and structural roles. The PDAC Stromal Reprogramming Consortium (PSRC) is a collaborative group of researchers working on pancreatic ductal adenocarcinoma (PDAC). Stromal reprogramming is when tumor cells communicate with non-cancerous cells in the stroma to cause changes in the tumor microenvironment that support the growth and protection of the tumor. One example of stromal remodeling is the growth of new blood vessels to supply oxygen and nutrients to the tumor.

Pancreatic cancers have a denser stroma than most tumors and this impedes treatments from reaching the cancer cells. PSRC researchers are identifying the elements in the tumor microenvironment that enable PDAC progression and impact PDAC response to therapy. These elements can serve as targets for therapeutics that could make the tumor more vulnerable to treatments.

Research programs supported by the NCI

Researchers funded by the NCI, located across the United States, are investigating questions about the basic biology of cancer and translating basic research findings into treatments that could be used clinically to detect or treat cancer. For example, researchers explore questions such as what are the molecules that control cell division and cell migration, how does a cell become cancerous and how does cancer evade the immune system. Basic research unveils molecules and processes that could be used as biomarkers to identify pancreatic cancer early or that may be targeted by cancer drugs. An NCI-funded program called Pancreatic Specialized Programs of Research Excellence (Pancreatic SPOREs) supplies grant money to help move basic research findings into the clinical setting.

The Pancreatic Cancer Cohort Consortium is a collaborative study investigating the causes and natural history of pancreatic cancer. Part of this investigation includes a genome-wide association study (GWAS) called PanScan. GWAS studies scan the complete set of DNA, or genome, of many individuals and look for genetic variants or regions where the genetic code varies between individuals. Researchers have used data from PanScan to the identify 20 regions in the human genome with genetic variants associated with pancreatic cancer risk. These variants could be used in the future to screen and detect pancreatic cancer earlier and may represent genes that can be targeted by drugs in patients affected by pancreatic cancer.

Pancreatic research programs in the UK

The National Cancer Research Institute (NCRI) is a partnership among cancer research charities and funding bodies in the United Kingdom. The NCRI Clinical and Translational Radiotherapy Research Working Group (CTRad) coordinates research on new radiotherapy technologies.

One of NCRI’s partners is the Pancreatic Cancer Research Fund (PCRF) which supports research to advance pancreatic cancer treatment and diagnosis. PCRF has established a tissue bank that collects high-quality pancreas tumor samples, a valuable resource for pancreatic cancer research. The UroPanc clinical study is developing a way to detect pancreatic cancer early using a urine test with the hope of enabling more pancreatic patients to catch their disease early when surgery is an option.

Pancreatic cancer studies are advancing the understanding of the biological mechanisms underpinning pancreatic cancer and leading to new drug targets and biomarkers for disease screening. Potential new treatments for pancreatic cancer are under investigation in clinical trials. They are an important potential treatment option that patients interested in enrolling should discuss with their treating physician.

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