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Targeting Aurora A Kinase Enhance the CDK4/6 Inhibitor Sensitivity in HR+/HER2- Breast Cancer

Juan Wu1,2, Yue Wang3, Honglin Yan1

  • 1Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China.

Oncology Research
|July 25, 2026
PubMed
Abstract

Insights

Targeting Aurora A kinase may overcome resistance to CDK4/6 inhibitors in breast cancer. Combining Aurora A inhibitors with CDK4/6 inhibitors shows synergistic antitumor effects, offering new therapeutic strategies for resistant breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are effective against HR+/HER2- breast cancer.
  • Treatment resistance to CDK4/6i remains a significant clinical challenge.
  • Understanding resistance mechanisms is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the role of Aurora A kinase in CDK4/6 inhibitor resistance.
  • To determine if targeting Aurora A kinase can enhance sensitivity to CDK4/6 inhibitors.
  • To explore the potential of combination therapy with Aurora A inhibitors and CDK4/6 inhibitors.

Main Methods:

  • Developed an Abemaciclib-resistant cell line (MCF7AR).
  • Assessed protein levels of p-RB, p-Aurora A, Aurora A, and USP22 in various samples.
  • Evaluated the efficacy of Aurora A inhibition using cell viability assays and xenograft experiments.

Main Results:

  • CDK4/6i-resistant cells and patient samples showed elevated phosphorylated Aurora A and RB levels.
  • High Aurora A activity counteracts spindle assembly checkpoint (SAC)-induced mitotic delay.
  • Combined Aurora A inhibitor and CDK4/6 inhibitor therapy demonstrated synergistic antitumor effects in vitro and in vivo.

Conclusions:

  • Aurora A kinase contributes to CDK4/6i resistance by promoting mitosis and overcoming SAC delay.
  • Aurora A inhibition may induce a synthetic lethal effect in RB-inactivated, CDK4/6i-resistant cells.
  • Targeting Aurora A kinase presents a promising strategy to overcome CDK4/6i resistance in breast cancer.
Keywords:
Aurora A kinaseCDK4/6i resistanceRB phosphorylationspindle assembly checkpointubiquitination

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