Aurora kinase A (Aurora-A), a
serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of
Aurora-A kinase occurs in different types of
cancer, including
lung cancer,
colorectal cancer, and
breast cancer. Alteration of Aurora-A impacts multiple
cancer hallmarks, especially, immortalization, energy metabolism, immune escape and cell death resistance which are involved in
cancer progression and resistance. This review highlights the most recent advances in the oncogenic roles and related multiple
cancer hallmarks of
Aurora-A kinase-driving
cancer therapy resistance, including chemoresistance (
taxanes,
cisplatin,
cyclophosphamide), targeted
therapy resistance (
osimertinib,
imatinib,
sorafenib, etc.), endocrine
therapy resistance (
tamoxifen,
fulvestrant) and radioresistance. Specifically, the mechanisms of
Aurora-A kinase promote acquired resistance through modulating DNA damage repair, feedback activation bypass pathways, resistance to apoptosis, necroptosis and autophagy,
metastasis, and stemness. Noticeably, our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1, ARID1A and MYC gene mutation
tumors, and potential synergistic strategy for mTOR, PAK1, MDM2,
MEK inhibitors or PD-L1
antibodies combined with targeting
Aurora-A kinase. In addition, we discuss the design and development of the novel class of Aurora-A inhibitors in
precision medicine for
cancer treatment.