Aurora kinase A

Overview

Aurora kinase A (AURKA) is a serine/threonine kinase encoded by the AURKA gene and is a critical regulator of mitotic progression in mammalian cells. It localizes to the centrosome and mitotic spindle, where it orchestrates centrosome maturation, bipolar spindle assembly, and accurate chromosomal segregation during cell division. Beyond its canonical mitotic functions, AURKA participates in a range of non-mitotic processes including DNA damage response, regulation of transcription factor activity, and cellular stress adaptation. Dysregulation of AURKA — most commonly through gene amplification or protein overexpression — is observed across a broad spectrum of human malignancies, including breast, colorectal, head/neck, melanoma, ovarian, liver, and prostate tumors, establishing it as both an oncogenic driver and a high-priority therapeutic target.

Structurally, AURKA contains an N-terminal regulatory domain and a C-terminal catalytic kinase domain. Its activity is tightly controlled through phosphorylation at Thr288 and interaction with co-activators such as TPX2. In oncological contexts, AURKA overexpression promotes tumor progression through multiple mechanisms: driving genomic instability, sustaining proliferative signaling via pathways including PI3K/AKT/mTOR, suppressing tumor suppressors such as PTEN, and interacting with oncoproteins such as MYCN. This multifaceted oncogenic role, combined with its well-defined ATP-binding pocket, has made AURKA an attractive focus for small-molecule inhibitors and, more recently, targeted protein degradation strategies.

Focus of Latest Publications

Recent publications have expanded interest in Aurora kinase A beyond its canonical role in mitotic progression, highlighting both catalytic and non-catalytic functions. Several studies used Aurora kinase A as a therapeutic target in cancer drug discovery, including PROTAC-based degradation, hydrophobic tag degraders, and selective small-molecule inhibition. In parallel, bioinformatic and molecular docking analyses identified Aurora kinase A among hub targets in multi-omics cancer signatures, supporting its continued relevance in multi-target anticancer strategies.

A notable theme is the emerging importance of Aurora kinase A degradation rather than inhibition alone. One study showed that PROTAC-mediated depletion of Aurora kinase A caused profound S-phase defects and revealed a scaffolding function in the S phase, with interactome profiling identifying RNA-binding proteins, including DICER, as well as altered chromatin association of SETD2. The authors proposed a dual-output model in which Aurora kinase A helps recruit RNA-binding proteins to R-loops and simultaneously recruits SETD2 to support resolution of replicative stress. Another study reported the discovery of M9101, a potent, selective, and in vivo active Aurora kinase A PROTAC degrader derived from a promiscuous kinase inhibitor, with strong degradation potency in MD-MBA-231 cells and exceptional selectivity in global proteomic analysis. In a related degradation-focused effort, norbornene-based hydrophobic tag degraders were developed against Aurora kinase A, and the broader HyT strategy was used to map degradable kinases across the human kinome.

Other recent work examined Aurora kinase A inhibition in specific cancer contexts. VIC-1911, a next-generation ATP-competitive Aurora kinase A inhibitor, was shown to suppress growth of prostate cancer cells, induce mitotic failure, DNA double-strand breaks, and p53 pathway activation, and to sensitize tumors to PARP inhibition by inducing a functional BRCAness phenotype. In pancreatic ductal adenocarcinoma, Aurora kinase A overexpression was linked to radioresistance through interaction with GSK3β and inhibitory phosphorylation of PTEN at T366, leading to activation of the PI3K/AKT/mTOR pathway; this phenotype was reversed by GSK3β knockdown or a PTEN-T366A mutant. In lung cancer, Aurora kinase A overexpression was associated with reduced response to immune checkpoint blockade, and mechanistic studies showed that Aurora kinase A promoted T-lymphocyte apoptosis through the NOXA/p4E-BP1/MCL-1 axis, compromising PD-1/PD-L1-mediated immune responses.

Aurora kinase A also appeared in broader computational and translational studies of cancer therapeutics. Multi-representation machine learning and structural-alert analyses were used to screen Aurora kinase A and Aurora kinase B inhibitors, with the goal of improving selectivity. In hepatocellular carcinoma, Aurora kinase A was identified as one of five major hub genes, and quercetin was reported to downregulate its expression in HepG2 cells while inhibiting cell viability. Across these studies, Aurora kinase A remains a prominent target in cancer biology, with recent publications emphasizing its roles in cell-cycle control, replication stress, DNA repair, radioresistance, and immune evasion, as well as its tractability for both inhibition and targeted degradation.

Key Publications

NEWJun AURORA A interacts with DICER and SETD2 to promote S-phase progression. (EMBO reports, 2026, PMID 42380670): "The oncogenic kinase AURORA A is essential for mitotic progression, and its catalytic inhibition arrests cells at the G2/M-transition."
Jun Multi-omics and pan-cancer analysis revealed common molecular signatures to disclose multitargeted anticancer agents through network pharmacology approach. (PloS one, 2026, PMID 42224282): "The protein-protein interaction (PPI) network study reveals the top-ranked, most significant hub targets, AURKA, CDK1 and CCNB1, as drug targets."
May Discovery of a Potent, Selective and In Vivo Active Aurora A PROTAC Degrader from a Promiscuous Kinase Inhibitor. (Journal of medicinal chemistry, 2026, PMID 42214088): "Here, we use Aurora A as a case study to demonstrate that proteolysis-targeting chimeras (PROTACs) provide a compelling solution to these challenges."
Jun Aurora A-Mediated Exosomal Secretion of miR-644a Promotes T-Lymphocyte Apoptosis Through the NOXA/p4E-BP1/MCL-1 Pathway. (Clinical and experimental pharmacology & physiology, 2026, PMID 42203488): "clinical evidence indicates that non-small-cell lung cancer (NSCLC) patients with elevated Aurora A expression exhibit reduced therapeutic responses to immune checkpoint blockade."
Jun Integrative bioinformatics and experimental validation reveal quercetin as a potential multi-target therapeutic agent in hepatocellular carcinoma. (Cytotechnology, 2026, PMID 42145839): "Among these, the five most significant hub genes-RFC4, TOP2A, AURKA, HSP90AA1, and MCM4-were selected for further analysis."
Jun Large-Scale Profiling of Kinase Degradation by Using Norbornene-Based Hydrophobic Tag (HyT) Strategy. (Angewandte Chemie (International ed. in English), 2026, PMID 42007494): "...we next rationally designed norbornene-based HyT degraders against ABL and AURKA, obtaining two optimized HyTs with potent degradation capabilities."
Mar Multi-representation machine learning approaches for screening aurora kinases A & B inhibitors and insights from structural alerts. (Journal of molecular graphics & modelling, 2026, PMID 41921419): "Aurora kinases A (AURKA) and B (AURKB) play a vital role, and their overexpression is linked to the aetiology of different carcinomas; thus, they are attractive targets for cancer treatment."
May AURKA inhibitor VIC-1911 induces mitotic defects and functional BRCAness, sensitizing prostate cancer to PARP inhibition. (JCI insight, 2026, PMID 41915443): "However, it has not been evaluated in prostate cancer (PCa), wherein AURKA is highly expressed in advanced stages and represents a critical therapeutic target."
Jun Design and synthesis of novel 1,2,4-triazolobenzene sulfonamide derivatives as selective CDK1 inhibitors with potent in vivo anticancer efficacy. (European journal of medicinal chemistry, 2026, PMID 41903286): "Among them, 11l emerged as a highly promising lead compound, exhibiting nanomolar inhibitory activity against CDK1 (IC50=5.5 nM) with high selectivity over CDK2, Aurora A, and CDK4, showing selectivity indices of 4.7-, 14.1-, and 73.2-fold, respectively."
May AURKA promotes radioresistance in pancreatic cancer via GSK3β-mediated PTEN phosphorylation at T366. (Experimental cell research, 2026, PMID 41864259): "In this study, it was demonstrated that the oncogenic kinase Aurora Kinase A (AURKA) drove radioresistance by orchestrating a signaling cascade that inhibited the tumor suppressor PTEN."