Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies.
Correlation of expression levels of these markers in the oral cancer cohort of The Cancer Genome Atlas (n = 313) with treatment outcome identified 54 genes (p < 0.05 or fold change >2) associated with disease recurrence, 8 genes (NQO1, UBE2C, EDNRB, FKBP4, STAT3, HOXA1, RIT1, AURKA) being significant with high fold change.
Expression of HPRT1, Jag2, AURKA, and PGK1 were elevated when compared to normal samples, and HPRT1 and PGK1 showed a stepwise elevation in expression that was significantly related to cancer grade.
SIGNIFICANCE: The identification of a synthetic lethal interaction between <i>RB1</i> and AURKA inhibition, and the discovery of a drug that can be dosed continuously to achieve uninterrupted inhibition of AURKA kinase activity without myelosuppression, suggest a new approach for the treatment of RB1-deficient malignancies, including patients progressing on CDK4/6 inhibitors.<i>See related commentary by Dick and Li, p. 169</i>.<i>This article is highlighted in the In This Issue feature, p. 151</i>.
The Cancer Genome Atlas data mining in the University of Alabama interactive web resource for pathways associated with poor survival of patients with adrenocortical carcinoma revealed significant upregulation of genes involved in DNA damage and regulation of cell-cycle pathways, such as AURKA, AURKB, CDK1, CDK4, CDK6, PLK1, CHEK1, CHEK2, CDC7, BUB3, and MCM3 (P < .001-.05).
SIGNIFICANCE: Dephosphorylation of FZR1 by PRL-3 facilitates the activity of APC/C<sup>FZR1</sup> by destabilizing AURKA, thus influencing aggressive characteristics and overall progression of colorectal cancer.
The tumor-suppressive miR-186 that is downregulated in neuroblastoma and in TGFβ-treated NK cells represses oncogenic proteins in neuroblastoma (MYCN and AURKA) and components of the TGFβ pathway.
A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers.
In the present study, the anticancer effects of cinobufagin were investigated on HCC Huh‑7 cells with mutant p53, and the effects of AURKA overexpression or inhibition on the anticancer effects of cinobufagin were analyzed.
Forced expression of the mitotic Aurora kinase A (AURKA), which promotes breast cancer metastases, failed to restore the invasive capacity of NOTCH3-null cells, demonstrating that NOTCH3 expression is required for an invasive phenotype.
Breast Cancer Risk Associated with Genotype Polymorphisms of the Aurora Kinase a Gene (AURKA): a Case-Control Study in a High Altitude Ecuadorian Mestizo Population.
Polymer Nanovesicle-Mediated Delivery of MLN8237 Preferentially Inhibits Aurora Kinase A To Target RalA and Anchorage-Independent Growth in Breast Cancer Cells.
In the present review, we will address the role of Aurora-A in cancer stem cells, as well as the outcomes of clinical trials assessing Aurora-A-specific small molecular inhibitors.
AURKA (aurora kinase A) has been identified as an oncogene in cancer development; however, its potential role and underlying mechanisms in the progression of BC remain unknown.
Mechanically, AURKA-mediated phosphorylation of LKB1 impairs LKB1 interaction with and phosphorylation of its downstream target AMPKα, which has critical roles in governing cancer cell energy metabolic homeostasis and tumorigenesis.
First, we demonstrate that SQ1274 has a much lower IC<sub>50</sub> than paclitaxel in both ARK1 (1.26 nM vs. 15.34 nM, respectively) and OVCAR8 (1.34 nM vs. 10.29 nM, respectively) cancer cell lines.
This study shows a novel synthetic lethality interaction between ARID1A and AURKA and indicates that pharmacologically inhibiting the AURKA-CDC25C axis represents a novel strategy for treating CRC with ARID1A loss-of-function mutations.
This study, first, confirms that AURKA influences deregulation of Wnt and Ras-MAPK signalling genes, and second, suggests mechanisms in CRC cell lines describing these interactions.