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.

Pancreatic Cancer Research Highlights

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 therapies to give to patients.

Testing treatments for early-stage pancreatic cancer

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

• 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.

Testing treatments for advanced pancreatic cancer

New treatments for metastatic pancreatic cancer that are being investigated in clinical trials are

• RAS-directed therapies 
  • the RAS genes make 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. Developing drugs that target mutant forms of RAS has proved challenging.
  • such drugs are now becoming available, such as a drug that targets a form of RAS that  has a mutation called G12C and another drug that targets a more common mutation, G12D. 
  • researchers have found that drugs blocking the activity of proteins that mediate the effects of RAS, force cancer cells to rely on a way of creating energy called autophagy. A study in mice found that a combination of two drugs shrank pancreatic tumors. One drug targets a protein that RAS works through, and the other drug blocks autophagy. Whether such combinations will be effective in pancreatic patients is still being studied.
• immunotherapy
  • pembrolizumab. A rare group of 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. Immune checkpoint inhibitors work by helping the patient's own immune system fight their tumor. Patients should ask to have their tumors tested for high MSI.
  • immune checkpoint inhibitor 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. For example, combining immune checkpoint inhibitors with a type of drug called  CD40 agonist (which helps activate T cells), has shown some evidence of benefit in patients with advanced pancreatic cancer.
  • combinations of drugs and treatments. Scientists are now studying combinations of immunotherapy drugs. They are also studying combinations of immunotherapy drugs with other treatments, such as radiation therapy, stromal modifying agents, and other targeted drugs.
  • natural killer cells. Natural killer cells (NK) cells are a type of white blood cell that can kill tumor cells or cells infected with a virus. NK cell therapies for pancreatic cancer are being tested in early-stage clinical trials. 
• stroma-modifying drugs
  • the stroma is the dense tissue around a tumor that does not contain cancer cells. It is mostly made up of connective tissue, blood vessels, lymphatic vessels, and nerves.
  • pancreatic cancers have much denser stroma than most tumors. Agents that help break down this stroma may help more chemotherapy drugs reach cancer cells. These drugs are being tested now.