advance and underscore the promise of immunotherapy in treating currently intractable cancers. Pancreatic Cancer According to U.S. estimates for the year 2023, 64,050 new cases of pancreatic cancer will be diagnosed and 50,550 people will die from the disease (28). Pancreatic cancer is a highly aggressive disease, with a 12 percent 5-year survival rate, and treatment options primarily limited to surgery, radiation therapy, and chemotherapy. Researchers are actively working to uncover novel ways to improve health outcomes for patients with pancreatic cancer. One of the ways to tackle this disease is to identify risk factors that can contribute to the development of pancreatic cancer. For example, a new diagnosis of diabetes, sometimes also called newonset diabetes, is a known risk factor for developing pancreatic cancer, although the reasons are not clear (717). Another active area of research is to develop safe and reliable methods of detecting pancreatic cancer early. Currently, USPSTF does not recommend screening for pancreatic cancer in individuals who do not have any symptoms of the disease (718). Ongoing studies are focused on developing prediction models and genetic tests to detect pancreatic cancer in individuals who are at high risk of developing the disease (719). Recent studies have also unveiled potential new drug targets for the treatment of pancreatic cancer. For example, one study found that pancreatic cancer meets its nutrient needs by using a metabolic pathway that is predominantly active in infants and is rarely used by normal cells in adults (722). When researchers blocked the pathway in preclinical animal models of pancreatic cancer with a therapeutic that blocks the metabolic pathway, tumor growth was severely inhibited (722). In another preclinical study, researchers found that pancreatic cancer cells use a different type of fuel, called uridine, when they do not have access to sugar, the most common type of fuel used by cells in the human body. Starving pancreatic tumors of uridine stopped tumors from growing (723). A recent scientific discovery revealed that pancreatic cancer cells make an abnormal form of a protein called collagen. Collagen is a protein in the extracellular space which provides structure to tissues and is found almost everywhere in the human body (724). The abnormal collagen produced by pancreatic cancer cells promotes tumor growth. When its production or function was blocked using a therapeutic in a preclinical animal model, cancer-fighting immune cells started to move into the tumors, and tumors shrank dramatically in response to a commonly used immunotherapy drug, which was otherwise not very effective in the presence of abnormal collagen (724). Findings of these preclinical studies are encouraging and pave the way to develop novel and effective treatment options for patients with pancreatic cancer in the near future. An in-depth understanding of the genetic makeup of pancreatic cancer has identified mutations in several genes, such as KRAS, that contribute to pancreatic cancer development (726). One KRAS mutation, called G12D, is the most common in pancreatic cancer and is present in about 35 percent of patients with pancreatic cancer. In the United States between 2001 and 2018, the incidence of pancreatic cancer more than doubled in younger women ages 15 to 34, compared to men of the same age range (38). ONGOING NCI INITIATIVES TO DEVELOP TESTS FOR EARLY DETECTION OF PANCREATIC CANCER • New Onset-Diabetes (NOD) Study aims to develop a blood test that can identify individuals with a new diabetes diagnosis who may need further testing for pancreatic cancer (720). • The Pancreatic Cancer Detection Consortium (PCDC) aims to develop a blood test that can identify early pancreatic cancer in averagerisk individuals. Researchers in PCDC are also working to improve imaging of the pancreas by developing methods that can pick up small deposits of tumor cells (721). In a preclinical study in an animal model of pancreatic cancer, combining two groups of immunotherapy drugs—one that activates the cancer-fighting T cells to move into the tumor and the other two that release the “brakes” from T cells and unleash them against cancer cells—significantly reduced tumor size in about half of the mice and the tumor disappeared completely in 25 percent of the mice (725). Envisioning the Future of Cancer Science and Medicine AACR Cancer Progress Report 2023 149
RkJQdWJsaXNoZXIy NTkzMzk=