Related Experiment Video

Updated: Jan 25, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

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Real-World Plasma Thymidine Kinase Activity in High-Risk and Metastatic Hormone Receptor-Positive, Human Epidermal

Thomas N O'Connor1, Emily Schultz1, Sheheryar Kabraji2

  • 1Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY.

JCO Precision Oncology
|January 23, 2026
PubMed
Abstract

Insights

Plasma thymidine kinase activity (TKa) shows promise as a biomarker for predicting response to cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy in hormone receptor-positive breast cancer. Lower TKa levels correlate with longer progression-free survival (PFS), indicating its potential to guide treatment decisions.

Area of Science:

  • Oncology
  • Biomarker Discovery
  • Breast Cancer Research

Background:

  • Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy are standard for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC).
  • Treatment response to CDK4/6 inhibitors varies among patients, necessitating reliable biomarkers for personalized treatment strategies.

Purpose of the Study:

  • To evaluate plasma thymidine kinase activity (TKa) as a prognostic and predictive biomarker for response to CDK4/6 inhibitor-based therapy.
  • To assess TKa in both early and advanced stages of hormone receptor-positive/HER2- breast cancer.

Main Methods:

  • Longitudinal assessment of plasma TKa levels at baseline, during treatment, and post-treatment.
  • Analysis of samples from 80 metastatic and 28 high-risk patients receiving CDK4/6 inhibitor therapy in the prospective Roswell Park Ciclib Study (NCT04526587).

Main Results:

  • In metastatic BC, baseline TKa inversely correlated with progression-free survival (PFS) (HR, 1.91; P=.03).
  • Patients with longer PFS (≥20 months) showed reduced on-treatment TKa compared to baseline, while those with shorter PFS (≤8 months) had higher on-treatment TKa.
  • In early-stage high-risk BC, on-treatment TKa levels were significantly lower than baseline (P=3.55e-08).

Conclusions:

  • Circulating TKa levels demonstrate potential as a continuous prognostic and predictive biomarker for CDK4/6 inhibitor therapy response.
  • Further research is warranted to establish definitive TKa cutoff values for informing clinical treatment decisions in breast cancer.

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