CDK4/6 inhibitors are targeted therapies commonly used as first-line treatments for patients with hormone receptor-positive HER2-negative (HR+/HER2-) metastatic breast cancer. However, some patients stop responding to CDK4/6 inhibitors, and the mechanisms behind this acquired resistance are poorly understood. In a new study led by Khandan Keyomarsi, Ph.D., researchers discovered that the inflammatory protein IL-6 becomes elevated in these patients, which then triggers another protein – STAT3 – that helps tumors progress.
This highlights the potential of monitoring IL-6 levels, which are easily measured in blood samples, as an early predictive biomarker for CDK4/6 inhibitor resistance, allowing physicians to guide patients toward more effective treatments. Further, the researchers also demonstrated that blocking the pathway using a STAT3 inhibitor stopped or slowed tumor growth in preclinical models of resistant cancer.