In brief
Australian researchers at the Garvan Institute of Medical Research found that higher activity of the protein CDK1 correlates with more aggressive estrogen‑positive breast cancers and poorer outcomes, potentially offering a biomarker for personalized treatment with CDK4/6 inhibitors. The study examined over 400 biopsy samples and was published in Advanced Science, although larger clinical trials are needed to confirm the findings.
SYDNEY, Oct. 31—A new study from Australia’s Garvan Institute of Medical Research indicates that the activity of a protein called CDK1 may help doctors predict which estrogen‑positive breast cancers will be resistant to a widely used class of targeted drugs, the CDK4/6 inhibitors.
Estrogen‑receptor‑positive (ER++) breast cancer is the most common subtype, and many patients receive a combination of hormone therapy and CDK4/6 inhibitors that block the cell‑division cycle. While these drugs can be highly effective in the early stages, most patients eventually experience disease progression, and the reasons why some tumors are less responsive remain poorly understood.
The Garvan team analyzed more than 400 breast‑cancer biopsy specimens, all from patients whose tumors expressed estrogen receptors. Each sample was evaluated for the activity of CDK1, a protein that drives the transition from the G2 phase to the M phase of the cell cycle. The researchers found that tumors with high CDK1 activity were markedly more aggressive and associated with poorer clinical outcomes compared to tumors with low CDK1 activity.
Importantly, the study also examined correlation between CDK1 activity and response to CDK4/6 inhibitors. In the subset of samples from patients who had received these drugs, higher CDK1 activity was consistently linked to shorter progression‑free survival, suggesting that CDK1 may serve as a predictive biomarker for drug resistance.
“Tracking a protein that drives cell division could help doctors tell which breast cancers are likely to respond to CDK4/6 inhibitors,” said a statement released by the Garvan Institute. The statement added that the findings “could inform more personalized treatment approaches for patients” and that larger clinical trials would be necessary to confirm the associations.
Beyond predictive value, the discovery may open a new therapeutic avenue. Current CDK4/6 inhibitors do not target CDK1, but the study noted that the high activity of this protein in resistant cancers could make it an attractive drug target. Development of agents that block CDK1 might provide an alternative strategy for patients whose disease has progressed on standard CDK4/6 therapy.
Experts caution that the study is still exploratory. The research was conducted on archival tissue samples rather than on patients actively receiving CDK4/6 inhibitors, and the authors emphasize that prospective, randomized trials are required before CDK1 testing can be incorporated into routine clinical practice.
Nevertheless, the work adds to a growing body of evidence that molecular profiling can refine treatment decisions in breast cancer. If validated, measuring CDK1 activity could help clinicians identify early which patients are likely to benefit from continued CDK4/6 inhibition and which may need alternative or additional therapies.
