Pancreatic cancer cells have a high level of a protein, called TGF-β, that can repress the activity of the immune system in fighting cancers. This research team can isolate tumor-specific killer T cells (called tumor-infiltrating lymphocytes, or TILs) from pancreatic cancer tissue and transfer them back to the patient for maximal impact against the tumor cells. The team is engineering TIL to make the cells resistant to the suppressive effect of TGF-β, potentially enabling the TIL to attack the cancer tissue within the pancreas.

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The standard of care for people with pancreatic cancer is difficult and often ineffective. To better control this type of cancer, the research team is testing a combination approach that involves shutting down two cellular pathways. The first pathway carries signals that relate to tumor growth, and the second controls a process called autophagy, in which the cell effectively reuses its own interior contents. By shutting down both pathways, the team hopes to slow or stop the growth of pancreatic tumors.

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Drugs called PARP inhibitors are being used to treat ovarian cancer by interfering with the processes of cell division that allows tumors to grow. The team is testing these drugs in pancreatic cancer in combination with other drugs that block cellular pathways also involved in DNA repair. It is hoped that together, these therapies will in many cases cause pancreatic tumors to shrink.

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Mutations in the KRAS oncogene drive the vast majority of pancreatic cancers. This research team is using knowledge of the immune system to isolate T cells that can target the cancer-promoting gene. This will allow the development of precision therapies involving highly selective white blood cells that can be given to pancreatic cancer patients to target and potentially destroy tumors.

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This team proposes the protein called integrin αvβ6 as a target for peptide receptor radionuclide therapy (PRRT), an approved molecular targeted therapy used to treat neuroendocrine tumors. αvβ6 is significantly increased in pancreatic cancer, especially in metastasis. The scientists have developed a radiolabeled αvβ6-targeting peptide that they have successfully used to image pancreatic cancer metastases. In this study they are developing and testing a similar peptide that can be used specifically to kill pancreatic cancer cells.

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The team is studying whether inhibiting cellular processes in pancreatic tumors can stop the out-of-control growth that is characteristic of cancer. Pancreatic cancers with mutations in the KRAS gene are weakened when a protein called SHP2 is blocked in the RAS pathway—a cellular pathway that may be essential to the growth of pancreatic cancer cells. Another means to block this pathway involves a protein called MEK. The team hopes that by inhibiting both of these components, they can slow down or stop the growth of pancreatic cancer tissue.

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Researchers on this team have identified a subpopulation of cells in pancreatic cancer that act like stem cells and help the cancer to proliferate. The team has also found that these cells are especially resistant to therapeutic drugs but may be sensitive to a new approach. The team is testing whether blocking a protein that regulates inflammation can slow or stop the growth of pancreatic cancer. Promising drugs in this class are already in development for autoimmune diseases, so if this approach is successful, doctors may be able to deploy it rapidly to develop new treatments for pancreatic cancer.

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