Researcher holding test tube

In Search Of: Early Diagnosis


Duke fellow Ryne Ramaker and clinician Jim Abbruzzese talk.
Hematology/oncology fellow Ryne Ramaker (left), and clinician Jim Abbruzzese aim to translate a potential early diagnostic test for pancreatic cancer from the lab to the clinic. Photo by Les Todd.

Pancreatic cancer is one of the most challenging types because it is most often diagnosed in the late stages, when surgery isn’t possible. In 2022, the five-year survival rate for the disease is 11%, a slight increase from last year, according to the American Cancer Society.

To make outcomes better, researchers around the world are trying to find a marker from blood or some other bodily fluid that would reliably diagnose pancreatic cancer in its early stages, said Jim Abbruzzese, MD, Duke Cancer Institute Distinguished Professor of Medical Oncology. Abbruzzese sees promise in a test that has been studied in the lab of Chris Counter, PhD, George Barth Geller Distinguished Professor of Pharmacology. Abbruzzese and hematology/oncology fellow Ryne Ramaker, MD, PhD, are beginning work to translate it to patients.

Counter’s lab tries to capture the moment when a normal cell progresses to a tumor, then study it. Even in a cancer with lots of successful treatment options, like melanoma, the best bet is still finding the disease early, said Counter, whose mother-in-law Linda Woolfenden died of melanoma. It’s even more important in a challenging disease like pancreatic cancer.

Siqi Li, PhD, now a Damon Runyan fellow at Fred Hutchinson Cancer Research Center, was a PhD student in Counter’s lab when she became intrigued by a method called maximum-depth sequencing, which was developed by researchers in the lab of Evgeny Nudler, PhD, at New York University to detect mutations that lead to antibiotic resistance in bacteria.

“Siqi saw the parallels between bacteria and cancer, and she was very interested in using this assay in mammals,” Counter said. “So she adapted this assay with the help of the lab of Dr. David McAlpine here at Duke for the mammalian genome to capture mutations causing cancer.”

Counter’s team found that this technology captures mutations that are too few and far between to be detected by traditional next-generation gene sequencing. “The assay was so sensitive, that Siqi was able to detect a cancer-causing mutation a week after mice were exposed to an environmental carcinogen,” Counter said. The team published results of this work in 2020 in the journal Nature Communications and in 2022 in the journal eLife. The studies were supported in part by a Duke Cancer Institute pilot grant, a program sustained by donor funds.

The test holds promise not only because of its sensitivity, but also because it’s specific to KRAS, a gene commonly mutated in pancreatic cancer, Abruzzese said.

Duke PhD student Siqi Li looks at the camera.
As a PhD student at Duke, Siqi Li conducted research that clinicians hope to translate into early detection of cancer-causing DNA mutation. Photo by Fred Hutchinson Cancer Research Center.

The translational studies, which were just funded by the National Cancer Institute, will try to find out whether the method can identify KRAS mutations in blood from a small number of patients already diagnosed with pancreatic cancer. Then the team will compare those results with those from traditional next-generation sequencing. Ramaker, the fellow, will work with Counter to evaluate and enhance the test and will talk to patients about joining the study. “My hope is to be involved in both ends and bridge the lab and the clinic,” he said.

“Because pancreas cancer is diagnosed usually at a later stage, we don’t have the opportunity to conduct many careful studies with patients who have earlier disease,” Ramaker said. “Earlier diagnosis and earlier understanding of the genetic profile will open up the door to think about the disease in a more nuanced way.”

This page was reviewed on 12/12/2022