UC Davis researchers, led by Julie Sutcliffe, have received a $3.3 million grant from the National Cancer Institute to advance efforts to diagnose pancreatic cancer before it spreads.
As part of the Pancreatic Cancer Detection Consortium (PCDC), the grant will fund efforts to perfect a peptide/radioactive fluorine combo molecule (18F-αvβ6-BP) that selectively binds to a cell surface receptor called αvβ6. Once injected into patients, positron emission tomography (PET) will be used to track the molecule as it homes in on tumors.
“The receptor we are targeting is expressed on pancreatic cancer cells,” said Julie Sutcliffe, professor of Internal Medicine and Biomedical Engineering and the project’s principal investigator. “It’s a marker for cancer aggression and not just in pancreatic cancer. There are applications in ovarian, head and neck, breast, colon, cervical and other cancers.”
Because it offers indistinct early symptoms, pancreatic cancer often goes undetected until after it has metastasized. The five-year survival rate for patients diagnosed at stage III is 3 percent. The rate for stage IV patients is 1 percent.
To combat these dreadful statistics, Sutcliffe’s team has focused for more than a decade on the αvβ6 receptor, which has been implicated in metastasis. They have taken a peptide that selectively binds to the protein and attached a fluorine-18 isotope to light up in the PET scan.
“If the cancer is metastasized, the tumor cannot be surgically removed,” Sutcliffe said. “Unfortunately, current imaging is frequently inaccurate and patients undergo needless exploratory surgery to identify the metastatic disease. If we could image this, we could see if the patient has disease in the pancreas, liver, lungs – wherever it has spread. We could determine if surgery will actually help the patient.”
Early results have been promising. A small clinical trial with nine patients, who had already been diagnosed with cancers of the pancreas, lung, breast or colon, has shown promising results. Now, the researchers want to test whether this approach can detect cancer earlier in its progression, even catching healthy cells as they transition into cancer cells.
A marker-based imaging test could profoundly impact the ability to detect pancreatic cancer before it metastasizes. In particular, this technique could benefit patients with familial pancreatic cancer or cystic lesions.
“People with familial pancreatic cancer are at higher risk, but there’s no way to tell unless you biopsy them,” said Sutcliffe. “But you’re not going to randomly biopsy people who have not been diagnosed. Also, some patients present with cystic lesions. These lesions may or may not become cancer, but right now we can’t tell the difference. We have to treat them like cancer, and that can lead to extra surgeries.”
In addition to UC Davis, the PCDC includes Mayo Clinic, Johns Hopkins University, Dana Farber Cancer Institute and other institutions. The grant gives the UC Davis team access to a variety of PCDC resources.
“This is a really dynamic group of investigators,” Sutcliffe said, “and we believe we can make a lot of progress towards an effective early-detection method.
The project, “Peptide-based targeted molecular imaging for early detection in pancreatic cancer,” is funded by the National Cancer Institute, grant 1UO1CA217665-01.