Aurora Kinases in Cancer: Mitotic Regulators as Drug Targets

Three Kinases, Different Locations

Aurora A localises to centrosomes and spindle poles, where it drives centrosome maturation, mitotic entry and bipolar spindle assembly. Aurora B is the enzymatic core of the chromosomal passenger complex, moving from centromeres to the spindle midzone and controlling attachment-error correction and cytokinesis.

Aurora C is expressed mainly in germ cells and has a role in meiosis, with limited relevance to most cancers.

How They Contribute to Cancer

AURKA sits within the 20q13 region that is amplified in breast, ovarian, gastric, pancreatic and other cancers. Excess Aurora A causes centrosome amplification and multipolar divisions, feeding chromosomal instability.

Aurora A also has functions outside mitosis, including stabilising the MYC and N-MYC oncoproteins, which has drawn particular interest in MYCN-amplified neuroblastoma and small-cell lung cancer.

Aurora B and Error Correction

Aurora B destabilises incorrect kinetochore-microtubule attachments so they can be remade correctly, and it sustains the spindle-assembly checkpoint signal while errors persist.

Inhibiting Aurora B forces cells through division with uncorrected attachments, causing gross missegregation and, often, failure of cytokinesis that produces large polyploid cells.

Inhibitors in the Clinic

Alisertib is the most studied Aurora A-selective inhibitor and has shown activity in peripheral T-cell lymphoma and small-cell lung cancer in trials, though phase 3 results have generally not met their goals.

Pan-Aurora and Aurora B inhibitors are limited by neutropenia. No Aurora inhibitor is broadly approved, and development now focuses on selected biomarker-defined groups and combinations.

Interpretation Notes

AURKA amplification or high Aurora expression in a tumour report is a proliferation-associated finding. It is not, on current evidence, a validated predictive biomarker for routine treatment selection.

As with other copy-number calls, the assay, threshold and tumour purity affect the result.

Key Takeaways

• ·Aurora A controls centrosomes and spindle poles; Aurora B controls attachment correction and cytokinesis.
• ·AURKA amplification (20q13) drives centrosome amplification and can stabilise MYC.
• ·Aurora inhibitors such as alisertib have shown activity but no broad approval.
• ·High Aurora expression is a proliferation marker, not a validated treatment-selection test.