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Updated: Jun 14, 2025

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
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Aurora Kinase A Inhibition Potentiates Platinum and Radiation Cytotoxicity in Non-Small-Cell Lung Cancer Cells and

Huijie Liu1, Ayse Ece Cali Daylan1, Jihua Yang1

  • 1Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Cancers
|August 29, 2024
PubMed

Insights

Aurora kinase A (AURKA) inhibition enhances chemotherapy and radiation efficacy in non-small-cell lung cancer (NSCLC). Targeting AURKA may improve outcomes for NSCLC patients, especially when combined with immunotherapy.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Therapeutics

Background:

  • Non-small-cell lung cancer (NSCLC) survival rates for non-oncogene-driven tumors remain low, necessitating novel therapeutic strategies.
  • Aurora kinase A (AURKA) was identified as a potential mediator of cisplatin resistance in NSCLC.
  • Understanding AURKA's role in platinum and radiation sensitivity is crucial for improving NSCLC treatment outcomes.

Purpose of the Study:

  • To investigate the role of AURKA in platinum and radiation sensitivity in NSCLC.
  • To evaluate the effect of AURKA inhibition on immune checkpoint expression in NSCLC.
  • To determine the therapeutic potential of combining AURKA inhibitors with standard NSCLC treatments.

Main Methods:

  • Utilized multiple NSCLC cell lines and xenograft mouse models.
  • Assessed AURKA expression in patient tumor specimens.
  • Inhibited AURKA using alisertib and inducible knockdown.
  • Evaluated cytotoxic effects, DNA damage, apoptosis, senescence, and immune checkpoint expression (PD-L1, B7x, B7-H3, HHLA2).

Main Results:

  • 91.5% of NSCLC patient tumors showed AURKA expression, with 34% moderate-to-high.
  • AURKA expression increased after cisplatin treatment in NSCLC cells.
  • AURKA inhibition potentiated cisplatin and radiation efficacy, leading to tumor regression.
  • AURKA inhibition increased DNA double-strand breaks, apoptosis, and senescence.
  • AURKA inhibition upregulated PD-L1 and B7-H3 expression.

Conclusions:

  • AURKA inhibition enhances the efficacy of platinum-based chemotherapy and radiation in NSCLC.
  • AURKA inhibition modulates the expression of key immune checkpoints.
  • Combinatorial strategies involving AURKA inhibitors and chemo-immunotherapy warrant further investigation for NSCLC treatment.
Keywords:
NSCLCaurora kinase Aimmune checkpointsplatinumradiation

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