Research Sheds New Light on a Key Ovarian Cancer Biomarker

Early detection is essential for improving ovarian cancer outcomes. When caught at stage 1, ovarian cancer survival rates can exceed 90%. Yet most cases are found after the cancer has spread, dropping survival rates to 35%.

One of the primary tools for detecting ovarian cancer is a blood test measuring CA125, a protein biomarker linked to the disease. While this test plays an important role in monitoring response and recurrence it can detect only about 50% of early-stage ovarian cancers, leaving half of cases undiagnosed. What’s more, CA125 levels can fluctuate for reasons unrelated to cancer, such as endometriosis or even normal menstrual cycles. These false positives and false negatives create significant barriers to reliable early detection.

Rebecca Whelan, Ph.D., an associate professor of chemistry at the University of Kansas and member of The University of Kansas Cancer Center’s cancer biology research program, is working to change that. With a career dedicated to protein detection, she and her team are exploring ways to improve the CA125 test as well as develop new methods for identifying ovarian cancer biomarkers. Her work, recently featured on the cover of Cancer Research Communications, has led to a discovery that reshapes our understanding of CA125 itself.

A “beads-on-a-string” breakthrough

Despite the vital role of CA125 in the diagnosis and management of ovarian cancer, not much is known about the protein. In fact, since its initial discovery in 1981, no accurate structural model of the protein existed — until now. That is, until Whelan and her team leveraged a third-generation DNA sequencing technology called long-read sequencing. Previously, it was believed that the CA125 protein resembled a string of 63 beads. However, the team was shocked to find that the protein actually has 19 beads, not 63.

“We sequenced another cell line. And then another and another,” Whelan recalled. “Then we obtained banked tumor tissue and sequenced that. Each test showed that CA125 has 19 beads.”

This discovery has important implications. Knowing the true structure of the protein allows researchers to pinpoint why the test sometimes fails to detect cancer or produces false alarms. By studying each “bead,” Whelan’s team identified subunits that play an active role in the CA125 test and others that do not. These findings could lead to a more precise CA125 test, improving its sensitivity and reliability.

Taking this a step further, Whelan and team fed the newly sequenced CA125 protein into an artificial intelligence system that predicts 3D protein models. They were able to generate detailed structural models, opening the door to innovations in ovarian cancer treatment.

“We can see the CA125 protein in ways we couldn’t before,” Whelan said. “The potential is extraordinary.”

The impact of collaboration

Whelan emphasizes the importance of teamwork in advancing ovarian cancer research. Her partnerships with experts in bioengineering and precision medicine, as well as patient research advocates, have brought new perspectives to the field.

For example, Whelan is collaborating with other researchers to discover new ovarian cancer biomarkers. She works closely with Andrew Godwin, Ph.D., deputy director of the cancer center, to study markers specific to the fallopian tubes, where many aggressive ovarian cancers originate. Their goal is to develop tools that target these markers and detects cancer before it spreads.

“There is a huge gap in ovarian cancer survivorship,” Whelan said. “By improving existing tests and developing new ones, we can catch the disease earlier, when survival rates are so much higher.”