Advances in Pancreatic Cancer Research

 Pancreatic cancer can be hard to treat surgically due to the location of the organ, and because the disease has often spread in the body by the time it is diagnosed.

Standard treatment for pancreatic cancer usually consists of surgery, chemotherapy, radiation, or combinations of each, depending on the cancer’s stage. Beyond these standard treatments, NCI scientists continue to look for ways to treat pancreatic cancer more effectively. Researchers are looking at the potential of new drugs, ways to combine standard drugs, and new modalities (such as immunotherapy) to give to patients.

Patients with pancreatic cancer are generally recommended to have both biomarker testing and testing for inherited genetic changes. Both types of testing can help suggest possible treatments and can indicate with a patient’s family members might have an increased risk for pancreatic cancer or other types of cancer.

Testing treatments for early-stage pancreatic cancer

Therapies for early-stage disease that are being tested in clinical trials right now include

• new adjuvant chemotherapy drug combinations
  Some of these postsurgical drug combinations are already known to extend the lives of patients with metastatic disease, but it's not clear if they are better at killing cancer cells left behind after surgery than standard treatments.
• neoadjuvant chemotherapy 
  This form of chemotherapy is given before surgery, with the goal of improving outcomes by shrinking the tumor before it’s removed. Pre-surgical chemotherapy also may help by killing cancer cells that have escaped from the tumor that would continue to grow as the patient recovers from surgery.
• cancer treatment vaccines 
  Cancer treatment vaccines help the body’s immune system recognize and destroy cancer cells. Cancer cells contain substances, called tumor-associated antigens, that are not present in normal cells or, if present, are at lower levels. Treatment vaccines can help the immune system learn to recognize and react to these antigens and destroy cancer cells that contain them.

  Testing treatments for advanced pancreatic cancer

  New treatments for metastatic pancreatic cancer that are being investigated in clinical trials include immunotherapy and targeted therapy. Immunotherapy uses substances to stimulate or suppress the immune system to help the body fight cancer. Targeted therapy uses drugs or other substances to target specific molecules that cancer cells need to survive and spread.

  Drug Targets Common Mutation in Pancreatic Cancer

  In mice, experimental drug MRTX1133 shrank pancreatic tumors with KRAS G12D mutations.

  • Targeted therapies 
    • Ras-directed therapies. The RAS genes makes proteins that take part in signaling pathways that control cell growth. Altered forms of these genes are found in more than 90% of pancreatic cancers. Drugs that target mutant forms of RAS are now being tested. One example is a drug that targets a form of RAS that  has a mutation called G12C and another drug that targets a more common mutation, G12D. 
    • olaparib. Olaparib (Lynparza) is used as maintenance therapy  in adults with metastatic cancer that has not progressed after platinum chemotherapy and has certain mutations in the BRCA1 or BRCA2 gene. 
  • Immunotherapy
    • pembrolizumab. In rare cases, people with pancreatic cancer have mutations in their tumor that cause high microsatellite instability (MSI). Pembrolizumab (Keytruda) is an immune checkpoint inhibitor approved for patients with pancreatic cancer that has high MSI. 
    • novel immune checkpoint inhibitors and combinations. Using one drug for immunotherapy treatment has not been effective for most people with pancreatic cancer. Therefore, researchers are combining several immunotherapies that can act on different parts of the immune system.
    • combinations of immunotherapy drugs with other treatments. These include radiation therapy, stromal modifying agents, and other targeted drugs.
    • cell therapies. Researchers are exploring the use of cell-based therapies for pancreatic cancer. These therapies use immune cells such as T cells and natural killer cells that are altered in the lab to kill cancer cells. 
  • Stroma-modifying drugs
    • the stroma is the fibrous tissue around a tumor that does not contain cancer cells. It is mostly made up of connective tissue, blood vessels, lymphatic vessels, and nerves. Some of these components can help to support cancer cells and/ or prevent the immune system from recognizing cancer cells.
    • pancreatic cancers have much denser stroma than most tumors. Agents that help break down or remodel this stroma may help more chemotherapy drugs reach cancer cells. Or they may help reduce cancer cell resistance to killing by other agents.

  For a list of specific drugs, see Drugs Approved for Pancreatic Cancer.