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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Friday, April 26, 2024
Aurora kinase inhibitors may mediate resistance to chemotherapy in patients with triple-negative breast cancer, according to research presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract LB061/22). Jia Xu, PhD, of the University of Alabama at Birmingham, and colleagues treated resistant triple-negative breast cancer cells with a combination of Aurora kinase inhibitors and anthracycline/taxane chemotherapy. They reported that Aurora kinase inhibition significantly enhanced the chemotherapy effect.
“Not all [patients with triple-negative breast cancer] respond to chemotherapy,” the investigators noted. “Identifying biomarkers to further predict and subdivide [these patients] with distinct chemotherapy responses and outcomes is very important.”
Using a reverse-phase protein array on MDA-MB-468 cells and MDA-MB-231 cells, the researchers found that the most significant protein changes after chemotherapy were phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which they noted fall into the mitotic kinase group. In addition, they reported that no significant change in the mRNA level was observed after chemotherapy, suggesting a post-transcription–level molecular mechanism may regulate the upregulation of AURKA and AURKB.
The investigators also observed that the protein level of AURKB decreased more significantly with cycloheximide treatment alone, compared with co-treatment with both cycloheximide and paclitaxel. According to the investigations, paclitaxel may have extended the lifetime of Aurora kinases and increased protein stability. Finally, they reported that AURKB and AURKA overexpression in triple-negative breast cancer cells rendered them resistant to paclitaxel treatment and reduced the apoptosis effect triggered by chemotherapy.
Disclosure: The study authors reported no conflicts of interest.
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