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Aurora kinase A (AURKA) is a critical serine/threonine kinase that regulates key stages of the cell cycle, particularly during mitosis. It is primarily localized to the centrosomes and spindle poles, where it facilitates centrosome maturation, spindle assembly, and the transition from G2 to M phase. AURKA is frequently overexpressed or amplified in a wide range of human malignancies, including breast, colon, and lung cancers, where it promotes genomic instability and aneuploidy. Beyond its role in cell division, AURKA is involved in non-mitotic pathways such as epithelial-mesenchymal transition (EMT) and the maintenance of cancer stem cell properties. Therapeutic strategies targeting AURKA involve small-molecule inhibitors like alisertib, which compete for the ATP-binding site to induce mitotic arrest and apoptosis. However, the clinical utility of these inhibitors is often limited by toxicities such as neutropenia and the challenge of identifying patients most likely to respond through specific biomarkers.
ATP-competitive inhibition of the kinase domain, inhibition of autophosphorylation at Thr288, and disruption of the AURKA-TPX2 interaction.
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