Furthermore, it was showed that the inhibitor specific for AURKB (AZD1152) can suppress CCNE1 expression in CRC cells and inhibit tumor cell growth. To conclude, this research demonstrates that AURKB accelerated the tumorigenesis of CRC through its potential to epigenetically activate CCNE1 expression, suggesting AURKB as a promising therapeutic target in CRC.

No abstract available

Moreover, our investigation has shown that AZD2014, SB505124, LJI308 and OSI-207 show a greater efficacy in patients in the low-risk category. Conversely, for the high-risk group patients, PD173074, ZM447439 and CZC24832 exhibit a stronger response...This innovative model provides a novel approach for forecasting prognosis and assessing drug sensitivity in HCC patients, driving a more personalized and efficacious treatment paradigm, elevating clinical outcomes. Nonetheless, additional research endeavours are required to confirm the model's precision and assess its potential to inform clinical decision-making for HCC patients.

P1/2, N=36, Recruiting, Chipscreen Biosciences, Ltd. | Phase classification: P1b/2 --> P1/2

No abstract available

In this study, we delved into the underlying mechanisms of specific BCR-ABL tyrosine kinase inhibitors (imatinib, nilotinib, ZM-306416, and AT-9283) in human melanoma A375P cells. Consequently, the expression of the E2F target genes (CCNA2, CCNE1, POLA1, and TK-1) was markedly suppressed in nilotinib and AT9283-treated A375P cells. In summary, our findings suggest that BCR-ABL tyrosine kinase inhibitors may regulate the G1-to-S transition in human melanoma A375P cells by modulating the RB-E2F complex.

Our research has demonstrated that DLGAP5 is upregulated in LUAD and exhibits a strong correlation with unfavorable prognosis. Furthermore, DLGAP5 assumes a significant function in the regulation of tumor immunity and treatment outcome of immune checkpoint inhibitors. Of note, we found that DLGAP5 promotes cell proliferation of LUAD via upregulating PLK1. Targeting DLGAP5 by AT9283, our newly identified DLGAP5 inhibitor, suppresses LUAD growth. DLGAP5 may become a promising prognostic biomarker and therapeutic target for patients with LUAD.

P1, N=36, Active, not recruiting, Oscotec Inc. | Recruiting --> Active, not recruiting

P1, N=14, Completed, Oscotec Inc. | Unknown status --> Completed | N=40 --> 14

P3, N=243, Recruiting, Advenchen Laboratories Nanjing Ltd.

AURKB inhibition may be a rational approach to augment the effectiveness of 5-FU chemotherapy in CRC.

Aurora B plays an essential role in CCA progression by modulating c-Myc stability and represents a new target for treatment and chemosensitization in CCA.

No abstract available

P1/2, N=50, Recruiting, Ellipses Pharma | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Sep 2023 --> Oct 2025

In conclusion, AURKB significantly influenced pathological retinal angiogenesis, thereby presenting a promising therapeutic target in ocular neovascular diseases.

Finally, cell-based studies suggested that Baicalin exhibited in-vitro cytotoxicity and anti-proliferative effects on lung cancer cell lines. Conclusively, Baicalin may be considered a promising therapeutic molecule against AURKB, adding an additional novel lead to the anti-cancer repertoire.

The reversal of the Warburg effect in BL cells and the subsequent inhibition of cell proliferation and induction of apoptosis were observed by targeting Aurora A and Aurora B with AT9283. This finding may present new therapeutic options and targets for BL.

In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A inhibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3R mutation...Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL.

Prophylactic treatment using antimitotic agents barasertib and vincristine significantly delayed the onset of tumor formation, reduced pre-malignant neuroblast hyperplasia, and prolonged survival in TH-MYCN mice. Moreover, combination therapy with antimitotic compounds and BCL2 inhibitors exploited mitotic stress induced by antimitotics and was synergistically toxic to neuroblastoma cell lines. These results collectively suggest that mitotic dysregulation is a key component of tumorigenesis in early neuroblasts, which can be inhibited by the combination of antimitotic compounds and pro-apoptotic compounds in MYCN-driven neuroblastoma.

12 patients received a prior FLT3 inhibitor including midostaurin, gilteritinib or sorafenib and 8/12 patients received ≥2 prior FLT3 inhibitors. Dose optimisation cohorts are continuing to identify the RP2D. Further cohorts are planned for evaluation of EP0042 in combination with standard of care therapies.

BI-847325 showed a broader range of activity than the MEK inhibitor GDC-0623. In conclusion, dual MEK/Aurora kinase inhibition shows remarkable potential for treating multiple types of hematological and solid tumors. The combination with capecitabine was synergistic in colorectal, gastric, and mammary cancer.

AT.9283, EXEL.2280, Gilteritinib, and Pracinostat had the largest correlation (absolute value) with a risk score. Four risk model genes (mRNAs), 12 miRNAs, and 21 lncRNAs formed an mRNA-miRNA-lncRNA network, containing HOXA10-hsa-miR-129-5p-LINC00689 and KIF18A-hsa-miR-221-3p-DANCR. Through bioinformatics, we constructed a prognostic model of m6A-associated anoikis genes in LGG, providing new ideas for research related to the prognosis and treatment of LGG.

This study established a promising HRCA-PDO biobank and conducted the first high-throughput and high-content HRCA drug screening in order to shed light on the prevention of colorectal cancer.

BCL2 inhibition overcomes intrinsic resistance and enhances sensitivity to AURKB inhibition in SCLC preclinical models.

Furthermore, like v-Src, treatment with the Aurora B inhibitor ZM447439 also caused Aurora B delocalization at concentrations that partially inhibited Aurora B autophosphorylation. Given that phosphorylation of Aurora B by v-Src was not observed, these results suggest that v-Src causes Aurora B delocalization by indirectly suppressing Aurora B kinase activity.

Furthermore, drug sensitivity assay showed that vorinostat inhibit CENPI expression and ACC cell growth. Additionally, si-RNA mediated knockdown of CENPI inhibited ACC cell growth and invasion and showed synergistic anti-proliferation effect with AURKB inhibitor barasertib. Pan-cancer analysis demonstrated that CENPI is a potential diagnostic and prognostic biomarker in various cancers as well as an anti-ACC therapeutic target.

Treatment with Palbociclib (CDK4 Inhibitor) and Barasertib (AURKB Inhibitor) inhibited HCC cell migration. Additionally, the PKRG high-risk group demonstrated higher infiltration levels of Naïve CD8+ T cells, Endothelial cells, M2 macrophage, and Tregs than the low-risk group. In summary, this study established the hepatocytes-related PKRG signature for prognostic stratification at the single-cell level by using machine learning algorithms in HCC and identified potential HCC treatment targets based on the PKRG signature.

Four drugs including metformin, BMS754807, Panobinostat, and AT9283 were screened out as potential hits with generally consistent inhibitory efficacy on HRCA-PDOs. This study established a promising HRCA-PDO biobank and conducted the first high-throughput and high-content HRCA drug screening in order to shed light on prevention of colorectal cancer.

To this end, we screened a library of kinase inhibitors in the PDAC cell lines PANC-1 and BxPC-3 and identified two highly potent molecules: Aurora kinase inhibitor AT 9283 (AT) and EGFR kinase inhibitor WZ 3146 (WZ)...Furthermore, combination therapy outcomes with gemcitabine/platinum drugs may also be more effective due to an increase in the NADH dehydrogenase complex...Additionally, novel therapy options, such as vimentin-antibody--drug conjugates, could be explored. Therefore, future studies with the two kinases as monotherapy/combination therapy are warranted.

Notably, the inhibition of Aurora A kinase by shRNA knockdown and treatment with Aurora A kinase inhibitors such as Alisertib, AMG900, or AT9283 upregulated LPCAT1 mRNA and protein expression in vitro. Aurora A kinase inhibition increased LPCAT1 expression and suppressed GBM cell proliferation. The combination of Aurora kinase inhibition with LPCAT1 inhibition may exert promising synergistic effects on GBM.

However, they display opposite effects, circ/linVRK1 favors apoptosis whereas circ/linMAN1A2 stimulates cell migration, and only XL765 did not alter the ratio of other dangerous circ/linRNAs in MCF-7. In MDA-MB-231 cells, AMG511 and GSK1070916 decreased circGFRA1, as a good response to drugs. Furthermore, some circRNAs might be associated with specific mutated pathways, such as the PI3K/AKT in MCF-7 cells with circ/linHIPK3 correlating to cancer progression and drug-resistance, or NHEJ DNA repair pathway in TP-53 mutated MDA-MB-231 cells.

This study demonstrates Chiauranib's positive efficacy toward NKTL through the activation of the AIF-dependent apoptosis pathway for the first time. The novel and multi-targets of Chiauranib and the synergistic effect with L-asparaginase may provide a promising therapy for NKTL patients.

At RP2D, AZD2811 was tolerable with G-CSF support. Neutropenia was a pharmacodynamic biomarker.

The cotreatment of cisplatin and barasertib suppressed tumor growth in the tumor mouse model. Thus, KDM5D might be involved in the development of persister cells, and AURKB disruption can overcome tolerance to platinum treatment in HNSCC.

The combined treatment of TTFields and AZD1152 led to a significant reduction in the number of ndGBM and rGBM cells compared to each treatment alone. Further evaluation of this approach, which has to be considered as a proof of concept, is warranted, before entering into early clinical trials.

Through high-throughput screening of a custom library of 276 compounds, we found that Aurora kinase B (AURKB) inhibitor, barasertib was more sensitive to the PR-S2 cells than H1993 cells...AURKB knockdown using multiple siRNA sequences increases the sensitivity to PHA665752 in the PR-S2 cells...AURKB inhibition induced BIMEL accumulation and reduced p-BIM expression. Collectively, our study suggests that AURKB activation induces resistance to MET-TKI through anti-apoptosis mechanism with upregulation of STAT3/BCL2 axis in MET-amplified lung cancer cells.

We demonstrate that combination of a Bcl-2 homology (BH)3-mimetic inhibitor (ABT-737), a selective inhibitor of Bcl-xL, Bcl-2, and Bcl-w, with alisertib or danusertib potently induces apoptosis through the Bcl-2 family effector protein Bax. On the other hand, we found Alisertib treatment causes activation of caspase-2, which promotes apoptosis by cleaving Bid into tBid, a suppressor of both Bcl-xL and Mcl-1. Together, these results define the Bcl-2 protein network critically involved in AURK inhibitor-induced apoptosis, and suggest that BH3-mimetics targeting Bcl-xL may help overcome resistance to AURK inhibitors in cancer cells.

P1b/2, N=3, Completed, Uma Borate | Recruiting --> Completed | N=80 --> 3

P1a, N=177, Completed, Sumitomo Pharma Oncology, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Jun 2022 | Trial primary completion date: Dec 2022 --> Jun 2022

Mechanistically, chiauranib suppresses the phosphorylation level of VEGFR2, which has an anti-t-FL effect by inhibiting the downstream MEK/ERK/STAT3 signaling cascade. In conclusion, chiauranib may be a potential therapy to treat t-FL, since it inhibits tumor growth and migration and induces apoptosis by altering the VEGFR2/ERK/STAT3 signaling pathway.

Here we show that human lung or mammary cells strikingly undergo SQM with polyploidisation when they are exposed to genotoxic or mitotic drugs, such as Doxorubicin or the cigarette carcinogen DMBA, Nocodazole, Taxol or inhibitors of Aurora-B kinase or Polo-like kinase. The results show that DNA damage has the potential to drive SQM via mitotic checkpoints, thus providing novel molecular candidate targets to tackle lung SCC. Our findings might also explain why SCC is frequent in the lung, but not in the mammary gland and why chemotherapy often causes complicating skin toxicity.