Roswell Park Team Exploring Promising Biomarker for Tracking Breast Cancer Response to CDK4/6 Therapy

Monitoring thymidine kinase activity levels may provide insights on response to treatment

Agnieszka Witkiewicz, MD

BUFFALO, N.Y. — Many patients with a common form of advanced breast cancer experience good responses when they’re treated with targeted drugs known as CDK4/6 inhibitors in addition to endocrine (hormone) therapy. But about 20% of patients don’t benefit, and many breast tumors ultimately prove resistant to this treatment approach. A team at Roswell Park Comprehensive Cancer Center is focusing on a new biomarker to help answer that question. Writing in the journal JCO Precision Oncology, they report that lower levels of thymidine kinase activity in the blood plasma, either before or during treatment, were associated with longer progression-free survival.

Monitoring this biomarker could help monitor a patient’s response to treatment and point the way to new strategies for tack ling treatment-resistant breast cancer, note the researchers, led by senior author Agnieszka Witkiewicz, MD, Professor of Oncology and Director of the Advanced Tissue Imaging Shared Resource at Roswell Park.

In collaboration with the biotech company Biovica International AB, Dr. Witkiewicz and colleagues analyzed data from an observational clinical trial of Roswell Park patients with hormone receptor positive/human epidermal growth factor receptor 2-negative (HER2-) breast cancer who received CDK 4/6 inhibitors — cyclin-dependent kinase 4/6 inhibitors — and endocrine therapy as standard-of care treatment.

CDK4/6 inhibitors block the cyclin-dependent kinases 4 and 6 (CDK4/6). CDK4 and 6 help can cer cells grow and divide, and also regulate TKa, an enzyme that is released into the bloodstream by actively dividing cancer cells, making high TKa levels a red flag for disease progression. The team used Biovica’s DiviTum TKa test to monitor TKa activity levels before and during treatment with CDK4/6 inhibitors. “It’s exciting to offer our patients a blood test that provides information about tumor cell proliferation, enabling us to moni tor the disease more closely,” says Dr. Witkiewicz, who notes that this testing is already being incorporated into treatment planning for many breast cancer patients at Roswell Park.

“These studies support using TKa monitoring or similar tests to better understand how tumors change during treatment and could suggest new strategies to prevent or treat breast cancers that resist treatment,” says Emily Schultz, MSc, a staff scientist in the Department of Molecular & Cellular Biology at Roswell Park and co-first author of the study.

The study was supported by funding from the National Institutes of Health/National Cancer Institute and the Roswell Park Alliance Foundation.