Pancreatic Cancer Treatment

Fighting Pancreatic Cancer with New Treatments

This grant proposal, led by Dr. Bin Zhang, is about finding better ways to treat pancreatic cancer. Most treatments, like chemotherapy, only help patients live a little longer (about 11 months on average), and new immune therapies that work for other cancers haven’t been successful for pancreatic cancer. Dr. Zhang’s team wants to change that by studying a combination of treatments to make them work better.

They’re focusing on a treatment called pelareorep (REO), which is a virus that attacks cancer cells with a specific mutation (called KRAS) and helps the immune system fight the cancer. When combined with drugs called checkpoint inhibitors (like anti-PD-1), REO shows some promise, but the cancer often becomes resistant. The team thinks this resistance happens because of a protein called osteopontin (OPN) and a pathway in the body called MAPK/ERK.  Here’s what they plan to do:

1. Test a New Drug Combo: They’ll use mice with pancreatic cancer to see if adding a drug called a MEK inhibitor (which blocks the MAPK/ERK pathway) makes the REO and anti-PD-1 treatment work better. They’ll check if tumors shrink and if the mice live longer.
2. Study the Immune System: They’ll look at how the treatment affects immune cells (like T cells) in the tumors to understand why it works or doesn’t. They’ll use advanced tools to see which immune cells are helping fight the cancer.
3. Learn About OPN: They think OPN helps cancer resist treatment by making immune cells less effective. They’ll test this by removing OPN from cancer cells or blocking it with a drug to see if it helps the treatment work better.
4. Check Human Samples: They’ll study tumor samples from pancreatic cancer patients who got REO and anti-PD-1 in a past clinical trial. They want to see if high levels of MAPK/ERK and OPN in these samples predict if the treatment will fail, which could help doctors choose the right patients for this therapy.

The team hopes their work will lead to better treatments for pancreatic cancer and other cancers with KRAS mutations, like colon cancer. They also want to find signs (biomarkers) to predict who will benefit from this treatment.  They’ll use high-tech tools to study tumors and immune cells in detail, and their findings could lead to new clinical trials to help patients live longer.

To learn more about past Researchers we’ve funded and their research findings, please check out Our Stewardship Report.

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